A Study to Compare the Efficacy and Safety of Fluticasone Furoate Nasal Sprays (FFNS) 55 Microgram (mcg) and 110 mcg in Chinese Pediatric Subjects With Allergic Rhinitis (AR)

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 4

Conditions: Rhinitis, Allergic, Perennial and Seasonal; Rhinitis, Allergic

Treatments: Other: Placebo; Drug: FFNS

Study type: Interventional

Funder types: Industry

Identifiers

NCT02424539

201492

Details and patient eligibility

About

This Phase IV interventional study is a multi-center, randomized, double-blind, placebo-controlled parallel study to evaluate the efficacy and safety of FFNS110 mcg and 55 mcg once daily versus vehicle placebo aqueous nasal spray in chinese pediatric subjects ages 2 to 12 years with AR.

This study comprises screening and run-in period (4 to14 days), double-blind treatment period (28 days) and follows up period (3 to7 days). Subjects entering the study will participate for maximum of 50 days, including five clinical visits and a follow-up contact.

The study is planned to enroll approximately 360 subjects.

Enrollment: 358 patients

Sex: All

Ages: 2 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed and dated informed consent obtained from the subject's parent/guardian.
• Chinese male or non-child bearing potential female pediatric outpatients subjects who are >=2 to <=12 years of age at Visit 2.
• Diagnosis of AR: Subjects must have a diagnosis of intermittent allergy rhinitis (IAR) [symptoms are present <4 days a week, or for <4 weeks] or persistent allergic rhinitis (PER) [symptoms are present >=4 days a week, or for >=4 weeks] by symptoms, physical signs skin prick test (SPT) and serum-specific immunoglobulin E (IgE) test. Subjects must have 2 or more symptoms of AR (watery rhinorrhea, nasal obstruction, nasal itching and sneezing), which are also present consecutively or accumulatively more than 1 hour on each day prior to Visit 1, or/and concomitant ocular symptoms: ocular itching, red eyes, watery eyes etc. The physical signs includes: nasal mucosa pale, oedema, nasal secretion. Allergic shiner and allergic crease in severity pediatric. A documented positive prick skin test and a positive serum specific IgE test using standardized allergen extract. A positive skin test is defined as a allergen wheal >=3 millimeters (mm), a histamine >=3 mm. Subjects have nasal symptoms described above or/and associated with ocular symptoms, as well as the nasal signs and one of laboratory test positive or demonstrate SPT represented a positive response or serum-specific IgE testing represented a positive response within 12 months prior to Visit 1.
• Subject must be willing to maintain same environment throughout the study.
• Subject and/or subject's parent/guardian understands and is willing, able and likely to comply with study procedures and restrictions as well as manage study drug administration.

Exclusion criteria

• Concomitant Medical Conditions: (a) Significant concomitant medical conditions defined as historical or current evidence of clinically significant uncontrolled disease of any body system. Significant is defined as any disease that, in the opinion of the investigator, would confound the interpretation of the study results if the disease/condition exacerbated during the study: significant renal impairment, which based on the opinion of the investigator, would preclude the subjects' participation in the study and current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). (NOTES: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis and Chronic stable hepatitis B and C [e.g., presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment] are acceptable if subject otherwise meets entry criteria). (b) A severe physical obstruction of the nose (e.g., deviated septum or nasal polyp) or frequent bleeding of the nose that could affect the deposition of double blind intranasal study drug. (c) Current or history of a Candida infection of the nose or oropharynx, shingles, chickenpox, measles, ocular herpes simplex. (d) Known hypersensitivity to corticosteroids or any excipients in the product. (e) Recent nasal septal surgery or nasal septal perforation. (f) Subjects start, discontinue or change desensitization treatment within 30 days prior to Visit 1. (g) Bacterial or viral infection of the eyes or upper respiratory tract within two weeks of Visit 1 or during the screening period. (h) Asthma, with the exception of mild intermittent asthma. (i) Diagnosis of rhinitis medicamentosa, vasomotor AR or eosinophil rhinitis.
• Abnormal Laboratory Findings: A clinically significant laboratory abnormality including Liver Function Tests at Visit 1 meeting the following criteria: Alanine aminotransferase (ALT) >2 x upper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
• Abnormal Electocardiogram (ECG): Clinically significant abnormal ECG finding at Visit 1. Significant is defined as: Corrected QT (QTc) > 450 milliseconds (msec) or QTc > 480 msec in subjects with Bundle Branch Block. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trail.
• Concomitant Medication: Use of prescription or over-the-counter medication that would significantly affect the course of AR, or interact with study drug, such as: Chronic use of concomitant medications such as tricyclic antidepressants, that would affect assessment of the effectiveness of the study drug; Chronic use of long- acting beta2-agonists (e.g., salmeterol); Potent Cytochrome P450 subfamily enzyme 3A4 [CYP3A4] inhibitors (e.g., ritonavir, ketoconazole, itraconazole, clarithromycin, etc); Allergen immunotherapy for the treatment of allergies.
• Use of followings medications are not allowed throughout the study: Short-acting antihistamines, including ocular preparations and antihistamines contained in anti-cold medicine, insomnia or antalgic; Oral or inhaled anticholinergics; Oral or intranasal decongestants; Oral or intranasal antileukotrienes; Oral or inhaled long-acting beta2 agonists; Chinese traditional medicines that have potential effect to AR; Liquorice preparation; Medications that significantly inhibit the CYP3A4, including ritonavir and ketoconazole; tricyclic antidepressants; long-acting antihistamines( eg. desloratadine, fexofenadine, cetirizine and loratadine [ taken as rescue medication]); Intranasal antihistamines; or Intranasal or ocular cromolyh; Intranasal corticosteroids includes: Inhaled, oral, intramuscular, intravenous, ocular and/or dermatological corticosteroid (with the exception of hydrocortisone cream/ointment, 1% or less) and Immunosuppressive medications; Subcutaneous omalizumab.
• Subjects will travel more than 48 hours during the study may cause the change of allergen.
• Subjects, who, in the opinion of the Investigator or sub-investigators, are not able to comply with the protocol requirements.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

358 participants in 3 patient groups, including a placebo group

FFNS 55 mcg Arm

Experimental group

Description:

Each subject will be dispensed with two nasal spray device labelled as Device A and Device B containing either FF or Placebo. Subject's on their own or with assistance from parent/guardian will administer FFNS 55 mcg per day, one intranasal spray from Device A, once daily into each nostril (27.5 mcg per spray) and another spray of placebo nasal spray from Device B, once daily into each nostril, in the morning for 4 Weeks.

Treatment:

Drug: FFNS

Other: Placebo

FFNS 110 mcg Arm

Experimental group

Description:

Each subject will be dispensed with two nasal spray device labelled as Device A and Device B containing FF or Placebo. Subject's on their own or with assistance from parent/guardian will administer FFNS 110 mcg per day, one intranasal spray from Device A, once daily into each nostril (27.5 mcg per spray) and another spray of placebo nasal spray from Device B, once daily into each nostril, in the morning for 4 Weeks.

Treatment:

Drug: FFNS

Other: Placebo

Placebo Arm

Placebo Comparator group

Description:

Each subject will be dispensed with two nasal spray device labelled as Device A and Device B containing only placebo. Subject's on their own or with assistance from parent/guardian will administer one intranasal spray of placebo, from Device A and Device B, once daily into each nostril in the morning for 4 Weeks.

Treatment:

Other: Placebo