A Randomised, Double Blind, Placebo Controlled, 4 Period, Incomplete Block, Crossover Study Assessing the Dose-response Curve of Fluticasone Propionate in an Antigen Challenge Chamber

NCT00848965 | Completed Phase 4 Results

• 2 other identifiers: 110341781 IIa
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Rhinitis, Allergic, Perennial; Allergic Rhinitis

Keywords

fluticasone propionate; Vienna Challenge Chamber; glucocorticosteroids; allergic rhinitis

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

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

Secondary Outcomes (6)

• 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

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Fluticasone propionate 25ug

EXPERIMENTAL

Drug: Fluticasone propionate

Fluticason propionate 50ug

EXPERIMENTAL

Drug: Fluticasone propionate

Fluticasone propionate 100ug

EXPERIMENTAL

Drug: Fluticasone propionate

Flutciasone propionate 200ug

EXPERIMENTAL

Drug: Fluticasone propionate

Interventions

Fluticasone propionate DRUG

Corticosteriod, with anti-inflammatory effects

Flutciasone propionate 200ug; Fluticason propionate 50ug; Fluticasone propionate 100ug; Fluticasone propionate 25ug

Placebo DRUG

Placebo comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• The contraceptive transdermal patch, such as norelgestromin / ethinyl estradiol transdermal system (if the subject is less than 89kg); or
• Double-barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm .
• Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; or
• An intrauterine device (IUD) or intrauterine system (IUS), inserted by a qualified physician,
• Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of less than 10 pack years.

You may not qualify if:

• 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.
• 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.
• The subject has taken prescription or non-prescription drugs, within 7 days prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety.
• History of alcohol/drug abuse or dependence within 12 months of the study. Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine).
• The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• The subject has donated a unit of blood (450 mL) within the previous 16 weeks or intends to donate within 16 weeks after completing the study.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Vienna, A-1150, Austria

Location

MeSH Terms

Conditions

Rhinitis, Allergic, Perennial; Rhinitis, Allergic

Interventions

Fluticasone

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 23, 2009
• Study Start: October 1, 2007
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: September 24, 2012
• Results First Posted: September 24, 2012

Record last verified: 2011-02

Locations

AU (1)