Clinical trial NCT00570492: Phase 4 Fluticasone Furoate Nasal Spray (VERAMYST) Long Term Pediatric Growth Study.
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Study to Evaluate the Effects of a One-Year Course of Fluticasone Furoate Nasal Spray 110mcg QD on Growth in Pre-Pubescent, Pediatric Subjects With Perennial Allergic Rhinitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rhinitis, Allergic, Perennial
Keywords: allergic rhinitis
fluticasone furoate nasal spray
growth
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-12-11
Enrollment: 474
Sex: ALL
Minimum age (years): 5
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to characterize, as accurately as possible, the estimation of the difference in pre-pubescent growth velocities between subjects treated continuously for one year with FFNS 110mcg QD, the highest dose approved for pediatric use in the US, and placebo nasal spray as determined by stadiometry.


Eligibility criteria: Inclusion criteria:

* Signed and dated informed consent obtained from the subject's legal parent/guardian. Adequate provisions for assent of children should be provided in accordance with the IRB and any local governance.
* Age: 5 to less than 7.5 years for females and 5 to less than 8.5 years for males at Visit 1.
* Subjects must have a diagnosis and history of perennial allergic rhinitis (PAR) as follows:
* At least a one year clinical history and treatment of PAR (written or verbal confirmation from the treating physician) and,
* A documented, positive skin test to an appropriate perennial allergen (animal dander, house dust mites, cockroaches and/or mold) or documented, historical, in vitro test results for a specific IgE (such as RAST, PRIST) within the past 12 months prior to Visit 1 will be allowed. A positive skin test during Visit 1 will also be allowed. A positive skin test is defined as a wheal 3mm larger than the diluent control for prick testing.

Note: Subjects who meet the above criteria and who may also have seasonal allergic rhinitis (SAR) and/or non-allergic rhinitis (NAR) are eligible for randomization.

* At Visit 2, the daily rTNSS on any 4 of the last 7 days prior to Visit 2 must be 5. Subjects should refrain from using rescue medication during the 7 days prior to Visit 2.
* Pre-pubescence: Tanner Staging equal to 1 for all classifications as assessed by the investigator during each of the five baseline study visits (Visit 1 through Visit 5). The same investigator should perform this assessment throughout the study for a respective subject, if possible, for consistency of assessment. Details are provided in the SPM.
* Current height measurement via standardized stadiometer is within the 3rd and 97th percentile according to the CDC and any local longitudinal standard height charts for age and gender as provided in the SPM (Visit 1 through Visit 5).
* Body weight and body mass index between the 3rd and 97th percentile according to the US CDC standards and any local standards as assessed during each of the five baseline study visits (Visit 1 through Visit 5). The US CDC standards are provided in the SPM.
* Compliance: Subject's parent/guardian is literate and both subject and parent/guardian are deemed capable of complying with all study procedures to include proper study drug administration, daily e-diary completion, in-clinic laboratory assessments, and in-home 24 hour urine collection during the 76 weeks of study participation (Visit 1 through Visit 5).

Exclusion criteria:

* A history or evidence of abnormal growth. Any previous or current condition that affects growth, including sleep disorders.
* Asthma, with the exception of mild intermittent asthma \[National Asthma Education and Prevention Program, 2007\] (Note: Subjects will be allowed to use short-acting inhaled beta2 agonists only on an as needed basis.)
* A history of nasal or sinus surgery, septal perforation, or severe obstruction in the nose (e.g. nasal polyps).
* Any other significant concomitant medical condition. 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. (Visit 1 through Visit 5)
* Any prior or current use of any medication/treatment that might affect growth including, but not limited to, methylphenidate hydrochloride, thyroid hormone, growth hormone, anabolic steroids, calcitonin, estrogens, progestins, biphosphonates, anticonvulsants or phosphate binding antacids. (Visit 1 through Visit 5).
* Use of corticosteroids, defined as:
* Inhaled, intranasal, or high potency topical (to include dermatological, optic and otic) corticosteroids within 6 weeks prior to Visit 1 or during the baseline period (Visit 1 through Visit 5).
* Systemic corticosteroids (to include oral and injectable) within 12 weeks prior to Visit 1 or during the baseline period (Visit 1 through Visit 5).
* Use of other allergy medications within an appropriate timeframe relative to Visit 1 to allow the medication to be eliminated or no longer producing an effect as well as during the baseline period (Visit 1 through Visit 5) including, but not limited to:
* Intranasal cromolyn - 14 days
* Short-acting prescription and OTC antihistamines - 3 days
* Long acting (second-generation) antihistamines (other than the loratadine syrup supplied by GSK to treat uncontrolled symptoms of PAR) including fexofenadine, cetirizine, desloratadine, and astemizole - 10 days
* Long-acting antihistamine: astemizole - 12 weeks
* Intranasal antihistamines (e.g. azelastine) -2 weeks
* Oral or intranasal decongestants - 3 days
* Intranasal, oral or inhaled anticholinergics - 3 days
* Oral antileukotrienes - 3 days
* Subcutaneous omalizumab - 5 months
* Immunotherapy initiated or adjusted within 30 days prior to Visit 1 or during the baseline period (Visit 1 through Visit 5) noting that no significant changes in the dose, concentration or dilution will be allowed during the study.
* Use of immunosuppressive medications 8 weeks prior to screening or during the baseline period (Visit 1 through Visit 5) of the study.
* Use of any medications that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazole. (Visit 1 through Visit 5)
* Allergy/Intolerance
* Known hypersensitivity to corticosteroids or any excipients in the nasal spray
* Known hypersensitivity to the antihistamine or decongestant being provided for worsening symptoms of rhinitis during the conduct of the study.
* Exposure to varicella (Chickenpox) or measles during the 3 weeks prior to screening or during the baseline period (Visit 1 through Visit 5), if non-immune. A diagnosis of varicella or measles during the baseline period is exclusionary as well.
* Recent exposure to an investigational study drug within 30 days prior toVisit 1.
* Affiliation with investigational site.
* Findings of a clinically significant, abnormal screening (Visit 1) clinical laboratory test.

Primary outcomes:
measure: Change From Baseline in the Growth Velocity of Pre-pubescent Pediatric Participants to the End of the 52-week Double-blind (DB) Treatment Period
timeFrame: Baseline Period (Weeks -16 to 0) and DB Treatment Period (Weeks 1 to 52)
Secondary outcomes:
measure: Mean 24-hour Urinary Free Cortisol Excretion
timeFrame: Randomization/end of 16-week Baseline Period (Week 0), End of 52-week DB Treatment Period (Week 52), and end of 8-week Follow-up Period (Week 60)
measure: Number of Participants With the Indicated Shifts From Baseline in Nasal Examination (NE) Results
timeFrame: Baseline Period (Weeks -16 to 0) and DB Treatment Period (Weeks 1 to 52)
measure: Mean Values for the Laboratory Parameters of Alkaline (Alk) Phosphatase (P), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Values for the Laboratory Parameters if Albumin and Total Protein
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Values for the Laboratory Parameters of Total Bilirubin and Creatinine
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Values for the Laboratory Parameters of Glucose, Calcium, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Hematology Values for Basophil, Eosinophil, Lymphocyte, White Blood Cell (WBC), Monocyte, Segmented Neutrophil (Neu), and Platelet Counts
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Values for Hemoglobin
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Values for Hematocrit
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Hematology Values for Red Blood Cells (RBCs)
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Values for Urine pH
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Mean Values for Urine Specific Gravity
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Number of Participants With the Indicated Urinalysis Results for Urine Bilirubin and Urine Nitrite
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Number of Participants With the Indicated Urinalysis Results for Urine Glucose, Urine Ketones, and Urine Proteins
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Number of Participants With the Indicated Urinalysis Results for Urine Occult Blood (OB) and the Urine Leukocyte Esterase Test (LET)
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
measure: Number of Participants With the Indicated Urinalysis Results for Urine Appearance (App.)/Clarity and Color
timeFrame: Baseline Period (Weeks -16 to 0), DB Treatment Period (Weeks 1 to 52), and Follow-up Period (Weeks 53 to 60)
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: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Riverside
country: United States
facility: GSK Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: GSK Investigational Site
state: California
city: Vista
country: United States
facility: GSK Investigational Site
state: California
city: Coral Gables
country: United States
facility: GSK Investigational Site
state: Florida
city: Ocala
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
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: Evansville
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facility: GSK Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Ypsilanti
country: United States
facility: GSK Investigational Site
state: Michigan
city: Plymouth
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Rolla
country: United States
facility: GSK Investigational Site
state: Missouri
city: Warrensburg
country: United States
facility: GSK Investigational Site
state: Missouri
city: Bellevue
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Canton
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: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Altoona
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Upland
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
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: El Paso
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
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: 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: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Nueve de Julio
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Charlottetown
country: Canada
facility: GSK Investigational Site
state: Prince Edward Island
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Trois Rivières
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Viña del Mar
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Laon
country: France
facility: GSK Investigational Site
city: Le Havre
country: France
facility: GSK Investigational Site
city: Montpellier
country: France
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Perugia
country: Italy
facility: GSK Investigational Site
state: Umbria
city: Lima
country: Peru
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Lee LA, Sterling R, Maspero J, Clements D, Ellsworth A, Pedersen S. Growth velocity reduced with once-daily fluticasone furoate nasal spray in prepubescent children with perennial allergic rhinitis. J Allergy Clin Immunol Pract. 2014 Jul-Aug;2(4):421-7. doi: 10.1016/j.jaip.2014.04.008. Epub 2014 May 21.