Clinical trial NCT01916226: A Comparator Study of Fluticasone Propionate Nasal Spray Verses (vs) Cetirizine in the Treatment of Seasonal Allergic Rhinitis
Official title: Study 200165, A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Compare the Efficacy of a 2-Week Treatment With Fluticasone Propionate Nasal Spray Versus Cetirizine in Adult Subjects With Seasonal Allergic Rhinitis (SAR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rhinitis, Allergic, Perennial and Seasonal
Keywords: cetirizine
seasonal allergic rhinitis
Quality of Life
fluticasone propionate nasal spray
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-08-05
Enrollment: 682
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase IV investigational trial is being conducted to evaluate the efficacy of a 2-week treatment of fluticasone propionate nasal spray (FPNS) vs. cetirizine on allergic nasal and ocular symptoms and quality of life in adult subjects with SAR. It is hypothesized that FPNS provides greater nasal symptom relief than cetirizine. The primary measure used to test this hypothesis is the change from baseline over two weeks in reflective total nasal symptom score (rTNSS) compared between FPNS and cetirizine. Approximately 648 subjects will be randomized into a 1:1:1:1 ratio of treatment allocation across approximately twenty-five to thirty-five sites in the US during the 2013 fall allergy season. All subjects will be outpatients. The total duration of study will be approximately 21 days including 7 days of screening period, and 14 days of treatment period.


Eligibility criteria: Inclusion Criteria

* Informed consent: Subject must give their signed and dated written informed consent to participate. Subject must understand and be willing, able, and likely to comply with study procedures and restrictions. Subject must be able to read, comprehend, and record information in English.
* Subject is treatable on an outpatient basis.
* Age: \>=18 years of age at Visit 1.
* Gender: Male or eligible female subjects. A female subject is eligible to participate if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, history of vasomotor symptoms. OR Childbearing potential with a negative pregnancy test at screening and agreeable to using one of the acceptable contraceptive methods consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study). An eligible female is also not lactating nor planning on becoming pregnant during the study.
* Diagnosis of SAR, defined as documented clinical history or physician verification of subject reported historical SAR during each of the last two fall allergy seasons and a positive skin prick test (wheal \>=3 millimeter \[mm\] larger than the negative control) to a prevalent local fall allergen within 12 months prior to Visit 1 or at Visit 1.
* Adequate exposure to local fall pollen: Subject resides within a geographical region where exposure to the local fall pollen to which they are sensitized is expected to be moderate or greater during the study period. Subject does not plan to travel outside the geographical region where exposure to local fall pollen to which they are sensitized is expected to be moderate or greater for more than 48 hours during the study period.

At Visit 2, the subject must meet the following criteria

* Eligible subjects will need to have moderate to severe SAR symptoms, defined as a morning rTNSS of \>=7 on at least four of the last seven days leading up to randomization. This includes the AM assessment on the morning of the randomization visit at Visit 2.
* Subjects should demonstrate at least a 70% compliance rate with both their placebo run-in study medications and their e-diary completion prior to randomization. This period includes the day of Visit 1 until the day before randomization at Visit 2.
* Subjects should have no significant change in medical condition(s) that would have been exclusionary at Visit 1.
* Subjects should not have used any prohibited medications that are detailed in the inclusion/exclusion criteria (including prohibited allergy medications).
* Subjects should not have travelled outside the local pollen region for more than 48 hours during the run-in period.

Exclusion Criteria

* Significant concomitant medical conditions, defined as but not limited to:

Historical or current evidence of a clinically significant uncontrolled disease of any body system (e.g., tuberculosis, psychological disorders, eczema, uncontrolled asthma). 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 intranasal study drug.

Nasal (e.g., nasal septum), ocular, or throat injury, or surgery to these areas in the last 3 months.

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 cataracts or ocular herpes simplex. Physical impairment that would affect subject's ability to safely and fully participate 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 four weeks prior to Visit 1 and during the treatment period. Inhaled, oral, intramuscular, intravenous, ocular, and/or dermatological corticosteroid (with the exception of hydrocortisone cream/ointment, 1% or less) within eight weeks prior to Visit 1 and during the treatment period.
* Use of allergy medications, within a timeframe relative to Visit 1, that would prevent the medication from being eliminated and/or have an effect. Exclusionary timeframes relative to Visit 1 for five common allergy treatments are noted below Intranasal cromolyn (\<=2 weeks from Visit 1). Intranasal or systemic decongestants (\<=3 days from Visit 1). Intranasal or systemic (other than oral) antihistamines (\<=3 days from Visit 1).

Leukotriene modifiers (\<=3 days from Visit 1). Oral antihistamines (\<=2 days from Visit 1). Allergy medications, other than study supplied medications, are not allowed during the study.

* Use of other medications that may affect allergic rhinitis or its symptoms, e.g., use of any ocular antihistamines, artificial tears, eyewashes/nasal irrigation solutions, homeopathic preparations, lubricants, sympathomimetic or vasoconstrictor preparations during the screening and treatment periods
* Use of any medications (prescription or non-prescription) or alcohol to induce sleep 48-hours prior to Visit 1 and during the treatment period.
* Use of other intranasally administered medications (e.g., calcitonin), including herbals and homeopathics during the run-in (Visit 1 - Visit 2) and treatment period.
* Use of immunosuppressive medications within 8 weeks prior to screening and during the treatment period.
* Use of any medications that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4 (e.g., ritonavir, ketoconazole) during the run-in (Visit 1 - Visit 2) and treatment period.
* Known hypersensitivity to corticosteroids or any excipients present in the nasal spray.
* Known hypersensitivity to cetirizine or any excipients in the tablet.
* Recent exposure to an investigational study drug or device within 30 days of Visit 1.
* Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.
* Chickenpox or measles during the last 3 weeks prior to screening and is non-immune.
* Immunotherapy is exclusionary unless the immunotherapy was initiated \>=30 days from 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.
* Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirement.

Primary outcomes:
measure: Mean Change From Baseline (CFB) in the Individual AM Reflective Total Nasal Symptom Scores (rTNSS) Over the Entire Treatment Period
timeFrame: Baseline through the entire treatment period (2 weeks)
Secondary outcomes:
measure: Mean Change From Baseline in the Individual AM Reflective Nasal Symptom Scores for Rhinorrhea, Nasal Congestion, Nasal Itching, and Sneezing Over the Entire Treatment Period
timeFrame: Baseline through the entire treatment period (2 weeks)
measure: Mean Change From Baseline in the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) Overall Score at Visit 3/Early Withdrawal.
timeFrame: Baseline and Visit 3 (Study Day 14 +/- 2 days)/Early Withdrawal
measure: Mean Change From Baseline in the AM Pre-dose Instantaneous Total Nasal Symptom Score (iTNSS) Over the Entire Treatment Period
timeFrame: Baseline through the entire treatment period (2 weeks)
measure: Mean Change From Baseline in the AM Pre-dose Reflective Total Ocular Symptom Score (rTOSS) Over the Entire Treatment Period
timeFrame: Baseline through the entire treatment period (2 weeks)
measure: Mean Change From Baseline in the AM Pre-dose Instantaneous Total Ocular Symptom Score (iTOSS) Over the Entire Treatment Period
timeFrame: Baseline through the entire treatment period (2 weeks)
measure: Mean Change From Baseline in the Combined Nasal and Ocular Reflective Total Symptom Score (rTSS = rTNSS+rTOSS) Over the Entire Treatment Period
timeFrame: Baseline through the entire treatment period (2 weeks)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Aventura
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
city: Owensboro
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Bethesda
country: United States
facility: GSK Investigational Site
state: Maryland
city: North Dartmouth
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Ypsilanti
country: United States
facility: GSK Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Columbia
country: United States
facility: GSK Investigational Site
state: Missouri
city: Rolla
country: United States
facility: GSK Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Bellevue
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
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: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
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: Greenfield
country: United States
facility: GSK Investigational Site
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Ford LB, Matz J, Hankinson T, Prillaman B, Georges G. A comparison of fluticasone propionate nasal spray and cetirizine in ragweed fall seasonal allergic rhinitis. Allergy Asthma Proc. 2015 Jul-Aug;36(4):313-9. doi: 10.2500/aap.2015.36.3860.