Clinical trial NCT00609674: A Clinical Study To Test A Nasal Spray (Fluticasone Furoate Nasal Spray) For The Treatment Of Perennial (Year-round) Allergic Rhinitis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Once-Daily Intranasal Administration of Fluticasone Furoate Nasal Spray 110mcg in Adult and Adolescent Subjects 12 Years of Age and Older With Perennial Allergic Rhinitis (PAR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rhinitis, Allergic, Perennial
Keywords: Perennial allergic rhinitis; fluticasone furoate nasal spray
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-02-07
Enrollment: 315
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the effects (effectiveness and safety) of an intranasal corticosteroid (fluticasone furoate nasal spray \[FFNS\]), with a placebo nasal spray for the treatment of perennial (year-round) allergic rhinitis.


Eligibility criteria: Inclusion Criteria:

Subjects eligible for enrollment in the study must meet all of the following criteria:

* Informed consent
* Subject has provided an appropriately signed and dated informed consent.
* An appropriately signed and dated assent must be obtained from the parents or guardian if the subject is a child under 18 years of age.
* Outpatient
* Subject is treatable on an outpatient basis.
* Age
* ≥ 12 years at Visit 2
* ≥ 18 years at Visit 1 for Russia and Germany
* Male or eligible female. Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test will be performed for all females of childbearing potential at Visits 1, 2, 5, and Visit 6/Early Withdrawal to determine if the subject is pregnant.

To be eligible for entry into the study, females of childbearing potential must commit to the consistent and correct use of an acceptable method of birth control, as defined by the following:

* Abstinence Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days).
* Oral contraceptive (either combined estrogen/progestin or progestin only),
* Injectable progestogen,
* Implants of levonorgestrel,
* Percutaneous contraceptive patches,
* Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year,
* Male partner who is sterile (vasectomy with documentation of azospermia) prior to the female subject's entry into the study and is the sole sexual partner for that female subject,
* Double barrier method-condom or occlusive cap (diaphragm or cervical /vault caps) plus spermicide,
* Estrogenic vaginal ring
* Diagnosis of PAR to include:
* A positive skin test (by prick method) response to appropriate perennial allergen (house dust mites, animal dander, mold, or cockroach) within last 12 months prior to Visit 1 or at Visit 1.

A positive skin test is defined as a wheal ≥3mm larger than the diluent control for prick testing.

* Two year medical history and past treatment of PAR (written or verbal confirmation) which includes perennial, i.e., year-round, symptoms. PAR symptoms would include nasal congestion, rhinorrhea, nasal itching and sneezing, eye itching/burning, eye tearing/watering, and eye redness.

In vitro tests for specific IgE (such as RAST, PRIST) will not be allowed for the diagnosis of PAR.

NOTE: Subjects who meet the above criteria for PAR and who also have a history of allergy to a seasonal pollen that will be present in their geographic area during study participation are NOT eligible for randomization.

* Environment
* Subject must be symptomatic to appropriate perennial allergen (animal dander, house dust mites, cockroach, mold) and willing to maintain same environment throughout the study.
* Ability to comply with study procedures
* Subject understands and is willing, able and likely to comply with study procedures and restrictions.
* Literate
* Subject must be able to read, comprehend, and record information in English or native language.

Randomization Criteria

At Visit 2, the subject must meet the following criteria:

* Average of the last 8 rTNSS assessments (4 AM assessments, 4 PM assessments) over the four 24-hours periods prior to randomization must be ≥6. This includes the AM assessment on the morning of the randomization visit.
* Average of the last 8 reflective nasal symptom assessments for congestion (4 AM assessments, 4 PM assessments) over the four 24-hour periods prior to randomization must be ≥2. This includes the AM assessment on the morning of the randomization visit.
* Average of the last eight rTOSS assessments (4 AM assessments, 4 PM assessments) over the four 24-hour periods prior to randomization must be ≥ 4. This includes the AM assessment on the morning of the randomization visit.
* The subject has demonstrated the ability to comply with the use of the daily e-diary, defined as completion of at least 80% of the assessments during the screening period.

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

* Significant concomitant medical conditions, defined as but not limited to:
* a historical or current evidence of clinically significant uncontrolled disease of any body system (e.g., tuberculosis, psychological disorders, eczema). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or which would confound the interpretation of the study results if the disease/condition exacerbated during the study.
* a severe physical obstruction of the nose (e.g., deviated septum or nasal polyp) or nasal septal perforation that could affect the deposition of double blind intranasal study drug
* nasal (e.g., nasal septum) or ocular injury/surgery in the last 3 months
* asthma, with the exception of mild intermittent asthma \[NAEPP, 2007; GINA, 2006\], or very mild asthma (Canada) \[Lemiére, 2004\].

NOTE: Subjects will be allowed to use short-acting inhaled beta2 agonists ONLY on an as needed basis.

* rhinitis medicamentosa
* bacterial or viral infection (e.g., common cold) of the eyes or upper respiratory tract within two weeks of Visit 1 or during the screening period
* documented evidence of acute or significant chronic sinusitis, as determined by the individual investigator
* current or history of glaucoma and/or ocular herpes simplex
* current cataract
* physical impairment that would affect subject's ability to participate safely and fully in the study
* clinical evidence of a Candida infection of the nose
* history of psychiatric disease, intellectual deficiency, poor motivation, substance abuse (including drug and alcohol) or other conditions that will limit the validity of informed consent or that would confound the interpretation of the study results
* history of adrenal insufficiency
* Use of corticosteroids, defined as:
* Intranasal corticosteroid within 4 weeks prior to Visit 1 (e.g., FLONASE™, VERAMYST, Nasonex, Rhinocort).
* Inhaled, oral, intramuscular, intravenous, ocular, and/or dermatological corticosteroid (with the exception of hydrocortisone cream/ointment, 1% or less, or equivalent) within 8 weeks prior to Visit 1.
* Use of other allergy medications within the timeframe indicated relative to Visit 1
* Intranasal or ocular cromolyn within 14 days prior to Visit 1 (e.g., Nasalcrom, Crolom)
* Short-acting prescription and non-prescription antihistamines, including ocular preparations and antihistamines contained in insomnia and "night time" pain formulations, within 3 days prior to Visit 1 (e.g., Benadryl, Chlortrimeton, Dimetane, Tavist)
* Long-acting antihistamines within 10 days prior to Visit 1, including loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine, terfenadine (e.g., Allegra, Claritin, Clarinex, Zyrtec)
* Long-acting antihistamine, astemizole, within 12 weeks prior to Visit 1
* Intranasal antihistamines (e.g., Astelin) within 2 weeks prior to Visit 1
* Oral or intranasal decongestants within 3 days prior to Visit 1 (e.g., Sudafed)
* Long-acting beta-agonists within 3 days prior to Visit 1 (e.g., SEREVENT™, Foradil)
* Intranasal, oral, or inhaled anticholinergics within 3 days prior to Visit 1 (e.g., Atrovent)
* Histamine H2-receptor antagonists including cimetidine, ranitidine, famotidine, nizatidine (e.g., ZANTAC™, Tagamet, Pepcid, Axid) within 1 day prior to Visit 1
* Oral antileukotrienes within 3 days of Visit 1 (e.g., Singulair)
* Subcutaneous omalizumab (Xolair) within 5 months of Visit 1
* Subjects are not permitted to use any artificial tears, eyewashes/nasal irrigation solutions, homeopathic preparations, lubricants, sympathomimetic or vasoconstrictor preparations during the screening and treatment periods. No exclusion period prior to screening (Visit 1) is required for these treatments.
* Use of other medications that may affect allergic rhinitis or its symptoms
* Chronic use of concomitant medications, such as tricyclic antidepressants, that would affect assessment of the effectiveness of the study drug
* Use of other intranasally administered medications (e.g., Miacalcin)
* Use of immunosuppressive medications eight weeks prior to screening and during the study
* Immunotherapy Immunotherapy patients may be enrolled in the study as long as the immunotherapy was not initiated within 30 days of Visit 1 and if the dose has remained fixed over the 30 days prior to Visit 1, and the dose will remain fixed for the duration of the study.
* Use of any medications that significantly alter the pharmacokinetics of fluticasone furoate, including ritonavir and ketoconazole
* Allergy/Intolerance
* Known hypersensitivity to corticosteroids, or any excipients in the product
* Use of contact lenses
* Use of Nasal Continuous Positive Airway Pressure (C-PAP) device (mask or pillow)
* Clinical trial/experimental medication experience
* Participation in a clinical trial within 12 months prior to Visit 1
* Participation in a previous or current FFNS (GW685698X) clinical study
* Positive pregnancy test or female who is breastfeeding
* Has a positive or inconclusive pregnancy test at Visit 1 or Visit 2
* Affiliation with investigational site
* Subject is a participating investigator, sub-investigator, study co-ordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned.
* Current tobacco use
* Subject currently uses, or has used within the past year, smoking products including cigarettes, cigars, and pipe or chewing tobacco.
* Chickenpox or measles
* A subject is not eligible if he/she currently has chickenpox or measles, or has been exposed to chickenpox or measles during the last three weeks and is non-immune. If a subject develops chickenpox or measles during the study, he/she will be withdrawn from the study. If a non-immune subject is exposed to chickenpox or measles during the study, his/her continuation in the study will be at the discretion of the investigator, taking into consideration the likelihood of developing active disease.
* Findings of a clinically significant, abnormal electrocardiogram (ECG)
* Findings of a clinically significant laboratory abnormality

Primary outcomes:
measure: Mean Change From Baseline Over the Entire Treatment Period in Daily Reflective Total Nasal Symptom Scores (rTNSS)
timeFrame: Daily; Baseline through End of Study (Week 4)
Secondary outcomes:
measure: Mean Change From Baseline Over the Entire Treatment Period in Morning (AM), Pre-dose Instantaneous Total Nasal Symptom Score (iTNSS)
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Mean Change From Baseline Over the Entire Treatment Period in Daily Reflective Total Ocular Symptom Scores (rTOSS)
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Total Nasal Symptoms: Mean Change From Baseline Over the Entire Treatment Period in AM rTNSS
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Total Nasal Symptoms: Mean Change From Baseline Over the Entire Treatment Period in PM rTNSS
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Total Nasal Symptoms: Mean Percent Change From Baseline Over the Entire Treatment Period in Daily rTNSS and AM, Pre-dose iTNSS
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Individual Nasal Symptoms: Mean Change From Baseline Over the Entire Treatment Period in Individual Daily Reflective Nasal Symptom Scores and AM, Pre-dose Instantaneous Nasal Symptom Scores for Rhinorrhea, Nasal Congestion, Nasal Itching, and Sneezing
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Mean Change From Baseline Over the Entire Treatment Period in Both Individual AM Reflective and PM Reflective Nasal Symptom Scores for Rhinorrhea, Nasal Congestion, Nasal Itching, and Sneezing.
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Total Ocular Symptoms: Mean Change From Baseline Over the Entire Treatment Period in AM, Pre-dose Instantaneous Total Ocular Symptom Scores (iTOSS)
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Total Ocular Symptoms: Mean Change From Baseline Over the Entire Treatment Period in Both the AM Reflective Total Ocular Symptom Scores (rTOSS) and PM rTOSS
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Total Ocular Symptoms: Mean Percent Change From Baseline Over the Entire Treatment Period in Both the Daily rTOSS and the AM, Pre-dose iTOSS
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Individual Ocular Symptoms: Mean Change From Baseline Over the Entire Treatment Period in Both the Individual, Daily Reflective and the AM, Pre-dose Instantaneous Ocular Symptom Scores for Eyes Itching/Burning, Eyes Tearing/Watering, and Eye Redness.
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Mean Change From Baseline Over the Entire Treatment Period in Both the Individual AM Reflective and PM Reflective Ocular Symptom Scores for Eyes Itching/Burning, Eyes Tearing/Watering, and Eye Redness
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Peak Nasal Inspiratory Flow (PNIF): Mean Change From Baseline in Daily, AM, and PM PNIF
timeFrame: Daily; Baseline through End of Study (Week 4)
measure: Mean Change From Baseline to Endpoint in the Rhinoconjunctivitis Quality of Life Questionnaire With Standardised Activities (RQLQ[S])
timeFrame: Baseline and Week 4
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Wheaton
country: United States
facility: GSK Investigational Site
state: Maryland
city: North Dartmouth
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Plymouth
country: United States
facility: GSK Investigational Site
state: Minnesota
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Lincoln
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Ocean
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: South Burlington
country: United States
facility: GSK Investigational Site
state: Vermont
city: Greenfield
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Saint John's
country: Canada
facility: GSK Investigational Site
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Kanata
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Trois Rivières
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: GSK Investigational Site
state: Saskatchewan
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Banska Bystrica
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Presov
country: Slovakia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Given JT, Cheema AS, Dreykluft T, Stillerman A, Silvey M, Wu W, Snowise NG, Philpot E. Fluticasone furoate nasal spray is effective and well tolerated for perennial allergic rhinitis in adolescents and adults. Am J Rhinol Allergy. 2010 Nov-Dec;24(6):444-50. doi: 10.2500/ajra.2010.24.3534.