Study FFR116365, an Open-label Study of GW685698X in Paediatric Subjects With Perennial Allergic Rhinitis

Study Overview
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Brief Summary
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Safety of GW685698X (55 µg/day, q.d.) nasal spray over a period of 12 weeks in Japanese paediatric subjects ages 2 to < 15 years with perennial allergic rhinitis will be evaluated. And secondarily, efficacy and systemic exposure of GW685698X (55 µg/day, q.d.) nasal spray over a period of 12 weeks in Japanese paediatric subjects ages 2 to < 15 years with perennial allergic rhinitis will also be evaluated.

Official Title
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Study FFR116365, an Open-label Study of GW685698X in Paediatric Subjects With Perennial Allergic Rhinitis

Conditions
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Rhinitis

Intervention / Treatment
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* Drug: Fluticasone furoate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent 2 to <15 years of age, male or eligible female (females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control), outpatient Diagnosis of perennial allergic rhinitis: A positive test response to house dust and/or dust mites on serum antigen-specific IgE antibody test at Visit 1. Six months or more clinical history of perennial allergic rhinitis. A positive test result on nasal eosinophil count at Visit 1/1A. Either subject's parent/guardian who signed ICF or subject is able to complete assessments on the patient diary through the study. ALT < 2xULN; alkaline phosphatase and bilirubin <= 1.5xULN Average of 3TNSS is >= 3.0 in the last consecutive 4 days prior to Visit 2. Completion of the patient diary on >= 3 days of the last consecutive 4 days prior to Visit 2 Exclusion Criteria: Has a seasonal pollen as an allergen A nose disorder that could affect the assessment of the study medication or eye or nose surgery (within 3 months prior to Visit 1) Bacterial or viral infection of upper respiratory tract or eye Concurrent disease/abnormalities: Clinically significant uncontrolled disease Known hypersensitivity to corticosteroids or any excipients in the investigational product Has recent participation in a study and/or exposure to an investigational study drug within 3 months prior to Visit 1 Use of the following medication and/or its combination drug within the specified time: Anti-IgE (Within 6 months prior to Visit 1), Immunosuppressive medications or Systemic corticosteroids (Within 8 weeks prior to Visit 1), Topical corticosteroids (Within 4 weeks prior to Visit 1), Immunotherapy or nonspecific allassotherapy which was initiated, discontinued or changed its dose within 4 weeks prior to Visit 1 Affiliation with Investigator's Site: Relative or employee History of alcohol or drug abuse, children in care or in the opinion of the investigator (sub-investigator), inappropriate to be enrolled in the study. Bacterial or viral infection of upper respiratory tract or eye during the screening period.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GW685698X<br>GW685698X 55mcg/day | Drug: Fluticasone furoate<br>* 55 mcg/day, intranasal, 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an other important medical event, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs (occurring at a frequency threshold >=5%) and SAEs. | From the start of study treatment (Visit 2) until follow-up contact (Visit 6) (up to 13 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophil Count at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. Basophils, eosinophils, lymphocytes, monocytes, and total neutrophil counts are measured as the percentage of cells in white blood cells. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Change From Baseline in Hemoglobin at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Change From Baseline in Platelet Count and White Blood Cell (WBC) Count at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Change From Baseline in Red Blood Cell (RBC) Count at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Change From Baseline in Hematocrit at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Change From Baseline in Albumin and Total Protein at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyltransferase (GGT) at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Change From Baseline in Direct Bilirubin, Total Bilirubin, and Creatinine at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Change From Baseline in Calcium, Chloride, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 4 and Week 12/Early Withdrawal | Change from Baseline was calculated as the value at the post-Baseline time points minus the value at Baseline. | Baseline, Week 4, and Week 12/Early Withdrawal | 
| Mean Change From Baseline in the 3 Total Nasal Symptom Score (3TNSS) Over the Entire Treatment Period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | The 3TNSS is the sum of the 3 individual symptom scores for sneezing, rhinorrhea, and nasal congestion. Each symptom is scored on a scale from 0 to 3; the range of sums for the 3TNSS is 0 to 9. The symptoms were evaluated using a scale of 0, 1, 2, or 3; a larger score indicates more severe symptoms. The participant's parent/guardian who signed the informed consent form (ICF) or the participant themself scored nasal symptoms every day during the screening period and the treatment period. The Baseline value is defined as the average 3TNSS over the last 4 consecutive days prior to Visit 2 (start of the treatment period). For the entire assessment period, a mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Change from Baseline was calculated as the mean score for the entire treatment period minus the score at Baseline. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Mean Percent Change From Baseline in the 3 Total Nasal Symptom Score (3TNSS) Over the Entire Treatment Period, Week 1to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | The 3TNSS is the sum of the 3 individual symptom scores for sneezing, rhinorrhea, and nasal congestion. Each symptom is scored on a scale from 0 to 3; the range of sums for the 3TNSS is 0 to 9. The symptoms were evaluated using a scale of 0, 1, 2, or 3; a larger score indicates more severe symptoms. The participant's parent/guardian who signed the informed consent form (ICF) or the participant themself scored nasal symptoms every day during the screening period and the treatment period. The Baseline value is defined as the average 3TNSS over the last 4 consecutive days prior to Visit 2 (start of the treatment period). For the entire assessment period, a mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Percent change from Baseline=(mean score at the post-Baseline assessment minus the score at Baseline) divided by the Baseline value * 100. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Mean Change From Baseline (BL) in Daily Variation of the 3 Total Nasal Symptom Score (3TNSS) | The 3TNSS is the sum of the 3 individual symptom scores for sneezing, rhinorrhea, and nasal congestion. Each symptom is scored on a scale from 0 to 3; the range of sums for the 3TNSS is 0 to 9. The symptoms were evaluated using a scale of 0, 1, 2, or 3; a larger score indicates more severe symptoms. The participant's parent/guardian who signed the informed consent form (ICF) or the participant themself scored nasal symptoms every day during the screening period and the treatment period. The BL value is defined as the average 3TNSS over the last 4 consecutive days prior to Visit 2 (start of the treatment period). For the entire assessment period, a mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Change from BL was calculated as the mean score for the entire treatment period minus the score at BL. Only those participants available at the indicated time points were assessed. | Baseline, Day 1 to Day 84 | 
| Mean Change From Baseline in the 4 Total Nasal Symptom Score (4TNSS) Over the Entire Treatment Period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | The 4TNSS is the sum of the 4 individual symptom scores for sneezing, rhinorrhea, nasal congestion, and nasal itching. Each symptom is scored on a scale from 0 to 3; the range of sums for the 4TNSS is 0 to 12. The symptoms were evaluated using a scale of 0, 1, 2, or 3; a larger score indicates more severe symptoms. The participant's parent/guardian who signed the ICF or the participant themself scored nasal symptoms every day during the screening period and the treatment period. The Baseline value is defined as the average of the 4TNSS in the last 4 consecutive days prior to Visit 2 (start of the treatment period). A mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Mean Percent Change From Baseline in the 4 Total Nasal Symptom Score (4TNSS) Over the Entire Treatment Period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | The 4TNSS is the sum of the 4 individual symptom scores for sneezing, rhinorrhea, nasal congestion, and nasal itching. Each symptom is scored on a scale from 0 to 3; the range of sums for the 4TNSS is 0 to 12. The symptoms were evaluated using a scale of 0, 1, 2, or 3; a larger score indicates more severe symptoms. The participant's parent/guardian who signed the ICF or the participant themself scored nasal symptoms every day during the screening period and the treatment period. The Baseline value is defined as the average of the 4TNSS in the last 4 consecutive days prior to Visit 2 (start of the treatment period). A mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Percent change from Baseline=(mean score at the post-Baseline assessment minus the score at Baseline) divided by the Baseline value * 100. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Mean Change From Baseline in the Total Ocular Symptom Score (TOSS) Over the Entire Treatment Period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | Symptoms of eye itching, tearing, and redness were scored by the participant's parent/guardian who signed the ICF or the participant themself using a scale of 0, 1, 2, or 3 (a larger score indicates more severe symptoms) and were recorded in the participant's diary. The TOSS is the sum of all three symtpom scores and ranges from 0 to 9. The mean of the Baseline period is defined as the mean score of 4 consecutive days prior to Visit 2 (start of the treatment period). The mean of each assessment period is defined as the mean score of the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12. For each assessment period, a mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Mean Percent Change From Baseline in the Total Ocular Symptom Score (TOSS) Over the Entire Treatment Period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | Symptoms of eye itching, tearing, and redness were scored by the participant's parent/guardian who signed the ICF or the participant themself using a scale of 0, 1, 2, or 3 (a larger score indicates more severe symptoms) and were recorded in the participant's diary. The TOSS is the sum of all three symtpom scores and ranges from 0 to 9. The mean of the Baseline period is defined as the mean score of 4 consecutive days prior to Visit 2 (start of the treatment period). The mean of each assessment period is defined as the mean score of the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12. For each assessment period, a mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Percent change from Baseline=(mean score at the post-Baseline assessment minus the score at Baseline) divided by the Baseline value * 100. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Mean Change From Baseline in Sneezing, Rhinorrhea, Nasal Congestion, and Nasal Itching Over the Entire Treatment Period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | Four individual symptoms (sneezing, rhinorrhea, nasal congestion, and nasal itching) were scored on a scale from 0 to 3 using a scale of 0, 1, 2, or 3; a larger score indicates more severe symptoms. The participant's parent/guardian who signed the ICF or the participant themself scored nasal symptoms every day during the screening period and the treatment period. The Baseline value is defined as the average of the symptom scores in the last 4 consecutive days prior to Visit 2 (start of the treatment period). A mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Mean Change From Baseline in Eye Itching, Tearing, and Redness Over the Entire Treatment Period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | Three individual symptoms (eye itching, tearing, and redness) were scored by the participant's parent/guardian who signed the ICF or the participant themself using a scale of 0, 1, 2, or 3 (a larger score indicates more severe symptoms) and were recorded in the participant's diary. The mean of the Baseline period is defined as the mean score of 4 consecutive days prior to Visit 2 (start of the treatment period). The mean of each assessment period is defined as the mean score of the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12. For each assessment period, a mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Mean Change From Baseline in the Score of Troubles With Daily Life Over the Entire Treatment Period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | The participant's parent/guardian who signed the ICF or the participant themself scored the participant's troubles with daily life once daily using the following scale: 0, None; 1, Few troubles; 2, Intermediate between 3 and 1; or 3, Painful and complicating daily life. The mean of the Baseline period is defined as the mean score of 4 consecutive days prior to Visit 2 (start of the treatment period). The mean of each assessment period is defined as the mean score of the entire treatment period, Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12. For each assessment period, a mean score for each participant was calculated using available diary data from the assessment periods, taking the average of non-missing data during the period. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline through the entire treatment period (12 weeks), Week 1 to 2, Week 3 to 4, Week 7 to 8, and Week 11 to 12 | 
| Number of Participants With the Indicated Scores for Rhinoscopy Findings (Swelling of Inferior Turbinate Mucosa, Color of Inferior Turbinate Mucosa, Quantity of Nasal Discharge, and Quality of Nasal Discharge) | Rhinoscopy was assessed by the investigator by scoring swelling of inferior turbinate mucosa (SOITM) scored as 0 (none), 1 (possible to see center of the middle turbinate), 2 (between 3 and 1), or 3 (impossible to see middle turbinate); color of inferior turbinate mucosa (COITM) scored as 0 (normal), 1 (pink), 2 (red), or 3 (pale); quantity of nasal discharge (QTND) scored as 0 (none), 1 (small amount adhered), 2 (between 3 and 1), or 3 (filled); and quality of nasal discharge (QLND) scored as 0 (none), 1 (pyoid), 2 (viscous), or 3 (watery). | Baseline, Week 4, Week 8, and Week 12/early withdrawal | 
| Number of Participants With the Indicated Overall Response to Therapy, as Assessed by the Investigator | The investigator evaluated the participant's overall response to therapy (defined as improvement in the symptoms of allergic rhinitis) compared with Visit 2 (start of the treatment period), using the following 7-point categorical scale: 1=significantly improved, 2=moderately improved, 3=mildly improved, 4=no change, 5=mildly worse, 6=moderately worse, and 7=significantly worse. | Week 12/early withdrawal | 
| Number of Participants With the Indicated Overall Response to Therapy, as Assessed by the Participant's Parent/Guardian or the Participant | The participant's parent/guardian who signed the ICF or the participant himself/herself evaluated the participant's overall response to therapy (defined as improvement in the symptoms of allergic rhinitis) compared with Visit 2 (start of the treatment period), using the following 7-point categorical scale: 1=significantly improved, 2=moderately improved, 3=mildly improved, 4=no change, 5=mildly worse, 6=moderately worse, and 7=significantly worse. | Week 12/early withdrawal | 
| Number of Participants With the Indicated Plasma Concentration of GW685698X for Participants Aged >=2 to <6 Years | Pharmacokinetic (PK) samples were collected to analyze the plasma concentration of GW685698X. | Between 0.5 to 2 hours after final dosing at Week 12 (Visit 5) | 
| Number of Participants With the Indicated Plasma Concentration of GW685698X for Participants Aged >=6 to <15 Years | PK samples were collected to analyze the plasma concentration of GW685698X. | Between 0.5 to 2 hours after final dosing at Week 12 (Visit 5) |