A Randomised, Double Blind, Placebo Controlled, 4 Period, Incomplete Block, Crossover Study to Assess the Dose-response Curve of Intranasal Fluticasone Propionate (25, 50, 100 and 200 μg, Once Daily for 8 Days) in the Vienna Challenge Chamber for the Purpose of Investigating the Sensitivity

GlaxoSmithKline1 site in 1 country59 target enrollmentOctober 2007

ConditionsRhinitis, Allergic, Perennial Allergic Rhinitis

InterventionsPlacebo Fluticasone propionate

DrugsFluticasone propionate Placebo

Overview

Phase: Phase 4
Intervention: Placebo
Conditions: Rhinitis, Allergic, Perennial
Sponsor: GlaxoSmithKline
Enrollment: 59
Locations: 1
Primary Endpoint: Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC)
Status: Completed
Last Updated: 13 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-centre, randomised, double-blind, four-period, incomplete block, crossover study, with 8 days repeat dosing of intranasal Fluticasone Propionate (25, 50, 100, 200ug) and/or placebo in the Vienna Challenge Chamber in subjects with allergic rhinitis.

Registry

clinicaltrials.gov

Start Date

October 2007

End Date

January 2008

Last Updated

13 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•The subject is healthy with the exception of seasonal allergic rhinitis. Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures.
•Males and females who are aged between 18 and 65 years of age.
•A female is eligible to enter and participate in the study if she is of:
•Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post menopausal. For the purposes of this study, post menopausal is defined as 1 year without menses (FSH/LH will be also tested to confirm menopausal status); or
•Child bearing potential, has a negative pregnancy test (urine) at entry, and agrees to one of the following acceptable contraceptive methods when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of a physician for the duration of the study - screening visit to follow-up contact):
•Complete abstinence from intercourse from the first visit, throughout the trial and for a minimum of 7 days after the completion of the trial; or
•Male partner was sterile prior to the female subject's entry into the study, or
•Implants of levonorgestrel inserted for at least 1 month prior to the study
•Injectable progestogen administered for at least 1 month prior to the study
•Oral contraceptive (combined or progestogen only) administered for a least one monthly cycle prior to study medication administration; or

Exclusion Criteria

•As a result of medical interview, physical examination or screening investigations, the principle investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 150 mmHg or a diastolic pressure above 90 mmHg unless the Investigator confirms that it is satisfactory for their age.
•The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness.
•Pregnant or nursing females.
•Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception as outlined (Inclusion Criteria 2)
•On examination the subject is found to have any structural nasal abnormalities or nasal polyposis, a history of frequent nosebleeds, recent nasal surgery or recent (within 2 weeks) or ongoing upper respiratory tract infection which in the Responsible Physician's opinion renders the subject unsuitable for participation in the study.
•Any respiratory disease other than mild stable asthma that is controlled with occasional use of as-needed short-acting beta-agonists and associated with normal lung function.
•The subject is likely to be unable to abstain from salbutamol use for 8 hours before a challenge.
•The subject has a screening QTcB value \>450msec (based on single or average QTc value of triplicate ECGs obtained over a brief recording period), PQ interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave). In addition subjects will be excluded if they have a history of atrial or ventricular arrhythmia.
•The subject has a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
•History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.

Arms & Interventions

Placebo

Intervention: Placebo

Fluticasone propionate 25ug

Intervention: Fluticasone propionate

Fluticason propionate 50ug

Intervention: Fluticasone propionate

Fluticasone propionate 100ug

Intervention: Fluticasone propionate

Flutciasone propionate 200ug

Intervention: Fluticasone propionate

Outcomes

Primary Outcomes

Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC)

Time Frame: Day 8 of each study period (Periods 1-4); up to Day 158

The TNSS (score of 0-12), defined as the sum of the symptom scores for nasal obstruction, rhinorrhea, nasal itch, and sneeze (each scored on 0-3 scale \[0=none, 1=mild, 2=moderate, 3=severe\]) was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours PSC. In the VCC, aerosolized allergen is administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.

Secondary Outcomes

Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)(Day 8 of each study period (Periods 1-4); up to Day 158)
Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)(Day 8 of each study period (Periods 1-4); up to Day 158)
Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)(Day 8 of each study period (Periods 1-4); up to Day 158)
Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge)(Day 8 of each study period (Periods 1-4); up to Day 158)
Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2(Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158)
Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2(Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158)