Intranasal SB-705498 in Non-allergic Rhinitis Patients

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

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

Study Overview

• Status: Completed
• Conditions: Rhinitis
• Intervention / Treatment: Drug: Placebo; Drug: SB-705498

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: August 25, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 23, 2011

Study Record Updates

• Last Update Posted (Estimate): December 1, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: NAR; Capsaicin challenge
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Picornaviridae Infections; Nose Diseases; Rhinitis; Common Cold
• Other Study ID Numbers: 111925

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 111925
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 111925
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 111925
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 111925
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 111925
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 111925
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: 111925
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register