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Intranasal SB-705498 in Non-allergic Rhinitis Patients

Phase 2
Completed
Conditions
Rhinitis
Interventions
Drug: Placebo
Registration Number
NCT01439308
Lead Sponsor
GlaxoSmithKline
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1Placebo3 incremental capsaicin doses
Arm 2SB-7054983 incremental capsaicin doses
Primary Outcome Measures
NameTimeMethod
Assessment of total symptom score (TSS) after unilateral, incremental dose, intranasal challenge with capsaicin0-4hours following dosing
Assessment of total Ipsilateral secretion's weight after unilateral, incremental dose, intranasal challenge with capsaicin0-4hours following dosing
Secondary Outcome Measures
NameTimeMethod
Intranasal, single dose SB-705498 plasma PK parameters- AUC(0-t)0-4hours post dosing
Number of participants with adverse eventsDay 1
Change from baseline in peak nasal inspiratory flow (PNIF) after unilateral, incremental dose, intranasal challenge with capsaicin0-4hours following dosing
Assessment of Total Contralateral secretion's weight after unilateral, incremental dose, intranasal challenge with capsaicin0-4hours following dosing
Number of participants with Individual Symptoms as assessed by TSS components after unilateral, incremental dose, intranasal challenge with capsaicin0-4hours
Soluble biochemical mediators, including but not limited to neuropeptides, in nasal secretions induced after unilateral, incremental dose, intranasal challenge with capsaicin0-4hours following dosing
Intranasal, single dose SB-705498 plasma PK parameters-Cmax0-4hours
Intranasal, single dose SB-705498 plasma PK parameters- Tmax0-4hours post dosing
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 rateDay 1
Number of participants with nasal examination dataDay 1
Number of participants with abnormal ECG findingsDay 1
Body temperatureDay 1
Number of participants with abnormal hematology valuesDay 1
Number of participants with abnormal clinical chemistry values- Carbon dioxide content/Bicarbonate, Cholesterol, Potassium, TriglyceridesDay 1
Number of participants with abnormal clinical chemistry values- CreatinineDay 1
Number of participants with abnormal clinical chemistry values- Gamma Glutamyl Transferase, Lactate DehydrogenaseDay 1

Trial Locations

Locations (1)

GSK Investigational Site

🇳🇱

Amsterdam, Netherlands

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