Clinical trial NCT00682643: A Clinical Study With Fluticasone Furoate Nasal Spray And Vehicle Placebo For The Treatment Of Perennial (Year-round) Allergic Rhinitis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter, Two-Year Study to Evaluate the Ocular Safety of Once-Daily, Fluticasone Furoate Nasal Spray 110mcg in Adults and Adolescents 12 Years of Age and Older With Perennial Allergic Rhinitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rhinitis, Allergic, Perennial
Keywords: Perennial Allergic Rhinitis
fluticasone furoate
ocular safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-05-22
Enrollment: 550
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 assess long-term ocular safety of fluticasone furoate nasal spray in adult and adolescent subjects diagnosed with perennial 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 of age and older at Visit 2

  * Male or eligible female Female subjects should not be enrolled if they plan to become pregnant during the time of study participation.

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 azoospermia) prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or
* Double barrier method-condom or occlusive cap (diaphragm or cervical /vault caps) plus Spermicide,
* Estrogenic vaginal ring. A urine pregnancy test will be done at the screening visit to confirm females of childbearing potential are not pregnant upon entry into the study. In addition, urine pregnancy tests will be done for all females of childbearing potential at each clinic visit.

  * 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 ³3mm 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 could include nasal congestion, rhinorrhea, nasal itching and sneezing.

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 and who also may have seasonal allergic rhinitis (SAR) and/or perennial non-allergic rhinitis (PNAR) are eligible for randomization.

* Environment

  •Subject must be symptomatic to appropriate perennial allergen (animal dander, house dust mites, cockroach, mold) and willing to maintain, as much as possible, the 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

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.
  * History or current diagnosis of diabetes mellitus
  * Uncontrolled hypertension (i.e., systolic blood pressure ³ 140mm Hg or diastolic blood pressure ³ 90mm Hg)
  * 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 6 months (including LASIK eye surgery)
  * Asthma, with the exception of mild intermittent asthma \[National Asthma Education and Prevention Program (NAEPP) Guidelines for the Diagnosis and Management of Asthma - Expert Panel Report 3, National Institutes of Health, August 28, 2007.

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 and/or previous history of cataract surgery
* 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
* History of Hepatitis B or C

  * Use of corticosteroids, defined as:
* Intranasal corticosteroid within 4 weeks prior to Visit 1 (e.g., VERAMYST, FLONASE™, Nasonex, Rhinocort).
* Inhaled, oral, intramuscular, intravenous, ocular, and/or topical corticosteroids (with the exception of topical hydrocortisone, 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 (e.g., Allegra, Claritin, Clarinex, Zyrtec).
* 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)
* Oral antileukotrienes within 3 days of Visit 1 (e.g., Singulair)
* Subcutaneous omalizumab (Xolair) within 5 months of Visit 1
* 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 8 weeks prior to screening and during the study
  * Immunotherapy Immunotherapy patients may be enrolled in the study if the immunotherapy was not initiated within 30 days of Visit 1, 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 (ritonavir and ketoconazole)
  * Use of chronic treatment with agents known to promote the development of cataracts (e.g., potassium-sparing diuretics and allopurinol)
  * Allergy/Intolerance
* Known hypersensitivity to corticosteroids or any excipients

  * Clinical trial/experimental medication experience
* Has recent exposure to an investigational study drug within 30 days of Visit 1
* Participation in a previous or current FFNS (GW685698X) clinical study

  * Positive urine 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.

  * Tobacco use
* Subject currently uses smoking products including cigarettes, cigars, and pipe or chewing tobacco, or has used these products in the last 6 months

  * 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 ECG
  * Findings of a clinically significant laboratory abnormality

Primary outcomes:
measure: Cumulative Proportion (CU) of Participants (Par.) With an Event, as Measured as a Percentage, for Posterior Subcapsular Opacity (P)
timeFrame: Baseline; Weeks 12, 24, 36, 52, 64, 76, 88, and 104
measure: Cumulative Proportion of Participants, as Measured as a Percentage, With an Intraocular Pressure (IOP) Event
timeFrame: Baseline; Weeks 12, 24, 36, 52, 64, 76, 88, and 104
Secondary outcomes:
measure: Change From Baseline in LOCS III Posterior Subcapsular Opacity at Week 52 and Week 104
timeFrame: Baseline, Week 52, and Week 104
measure: Number of Participants With the Indicated Change From Baseline in LOCS III Posterior Subcapsular Opacity by Increments of 0.1 at Weeks 52 and 104
timeFrame: Baseline, Week 52, and Week 104
measure: Change From Baseline in LOCS III Cortical Opacity (C) at Week 52 and Week 104
timeFrame: Baseline, Week 52, and Week 104
measure: Number of Participants With the Indicated Change From Baseline in Cortical Opacity by Increment Categories of >=0.3, >=0.5, and >=1.0 at Weeks 52 and 104
timeFrame: Baseline, Week 52, and Week 104
measure: Change From Baseline in LOCS III Nuclear Opacity (NO) at Week 52 and Week 104
timeFrame: Baseline, Week 52, and Week 104
measure: Change From Baseline in Nuclear Color (NC) at Week 52 and Week 104
timeFrame: Baseline, Week 52, and Week 104
measure: Change From Baseline in Intraocular Pressure (IOP) at Weeks 52 and 104
timeFrame: Baseline, Week 52, and Week 104
measure: Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) by Increments of 1 mm Hg at Week 52
timeFrame: Baseline and Week 52
measure: Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) by Increments of 1 mm Hg at Week 104
timeFrame: Baseline and Week 104
measure: Change From Baseline in Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity (VA) Using Early Treatment Diabetic Retinopathy Study (ETDRS) Charts at Week 52 and Week 104
timeFrame: Baseline, Week 52, and Week 104
measure: Percent Change From Baseline in the Funduscopic Horizontal Cup-to-disc Ratio at Week 104
timeFrame: Baseline and Week 104
measure: Change From Baseline in the Daily Reflective Total Nasal Symptom Score (rTNSS) for the Indicated Study Periods
timeFrame: Baseline, Weeks 1 to 26, Weeks 27 to 52, Weeks 53 to 78, and Weeks 79 to 104
Other outcomes:
Locations:
city: Oxford
country: United States
facility: GSK Investigational Site
state: Alabama
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Mission Viejo
country: United States
facility: GSK Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: GSK Investigational Site
state: California
city: Roseville
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: San Jose
country: United States
facility: GSK Investigational Site
state: California
city: Stockton
country: United States
facility: GSK Investigational Site
state: California
city: Vista
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Englewood
country: United States
facility: GSK Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: GSK Investigational Site
state: Colorado
city: Tallahassee
country: United States
facility: GSK Investigational Site
state: Florida
city: Conyers
country: United States
facility: GSK Investigational Site
state: Georgia
city: Gainesville
country: United States
facility: GSK Investigational Site
state: Georgia
city: Lawrenceville
country: United States
facility: GSK Investigational Site
state: Georgia
city: Stockbridge
country: United States
facility: GSK Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: South Bend
country: United States
facility: GSK Investigational Site
state: Indiana
city: Bethesda
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: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Bozeman
country: United States
facility: GSK Investigational Site
state: Montana
city: Bellevue
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Ocean
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Skillman
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Asheville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Sylvania
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Eugene
country: United States
facility: GSK Investigational Site
state: Oregon
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Summerville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: El Paso
country: United States
facility: GSK Investigational Site
state: Texas
city: Kerrville
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Waco
country: United States
facility: GSK Investigational Site
state: Texas
city: South Burlington
country: United States
facility: GSK Investigational Site
state: Vermont
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Greenfield
country: United States
facility: GSK Investigational Site
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: LaForce C, Journeay GE, Miller SD, Silvey MJ, Wu W, Lee LA, Chylack LT Jr. Ocular safety of fluticasone furoate nasal spray in patients with perennial allergic rhinitis: a 2-year study. Ann Allergy Asthma Immunol. 2013 Jul;111(1):45-50. doi: 10.1016/j.anai.2013.04.013. Epub 2013 May 12.