Fall Epidemic Viral Pediatric Study

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01192178
• Collaborator: (none)
• Enrollment: 339
• Locations: 38
• Arms: 2
• Duration (Months): 4
• Patients Per Site: 8.9
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

Study ADA113872 is an exploratory 16-week multi-centre, randomized, double-blind, parallel group study in pediatric subjects, 4 to 11 years of age, with a history of seasonal asthma exacerbation(s). Approximately 40 clinical sites in the United States will randomize 316 subjects. Eligible subjects will be randomly assigned to one of two double-blind treatments using a 1:1 randomization. Subjects will be identified for their eligibility for enrolment starting in April 2010. Eligible subjects will be invited to return for randomization into the study in August 2010. This exploratory study is being conducted to assess whether treatment with ADVAIR™ DISKUS™ 100/50 mcg is more effective at reducing the risk of exacerbation and the asthma impairment associated with viral respiratory tract infections during the fall season when compared to treatment with FLOVENT™ DISKUS™ 100 mcg.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: FLOVENT™ DISKUS™ 100 mcg BID; Drug: ADVAIR™ DISKUS™ 100/50 mcg BID	Phase 4

Detailed Description

Study ADA113872 will assess the ability of ADVAIR™ DISKUS™ 100/50 mcg, in comparison to FLOVENT™ DISKUS™ 100 mcg, to reduce worsening asthma associated with viral respiratory infections during the fall season in a pediatric population. A number of descriptive measures will be used to assess the reduction in worsening asthma. These include the number of exacerbations, the duration and severity of asthma symptoms in the 7 days following the report of moderate upper respiratory tract symptoms or worsening asthma, the number of rescue-free days, and the rate of asthma control days.

Subjects will be identified starting in April 2010 to evaluate whether they meet the eligibility criteria. If a subject is identified as a potential candidate for the study they will be requested to return to the clinic between August 2, 2010 and August 20, 2010. Subjects who meet all inclusion and none of the exclusion criteria will be entered into the study. All subjects must be randomized on or before August 20th, 2010.

Subjects will be males and females who are between the ages of 4 and 11 years (as of randomization date) with a documented diagnosis of asthma requiring ICS monotherapy controller medication or low dose ICS as part of combination controller medication. In order for a subject on moderate dose ICS or low dose ICS + LABA combination therapy to be eligible for inclusion in this study their asthma must be under control for the 3 months prior to randomization and they must be a candidate for step-down therapy as outlined by current asthma management guidelines.

All subjects must have a history of one or more exacerbations during the previous respiratory viral season that required the use of outpatient oral/parenteral corticosteroid or an urgent care, Emergency Department visit hospitalization, or for asthma that required the use of oral/parenteral corticosteroid.

Subjects will receive their study medication at the Randomization visit and be instructed to keep an electronic daily record of AM PEF, asthma symptoms, night-time awakenings due to asthma, rescue use, and upper respiratory tract infection symptoms.

During the double-blind treatment period the electronic Diary (eDiary) will alert the subject or parent/legal guardian when the data imputed into the eDiary indicates the presence of upper respiratory symptoms of moderate or severe severity or if the subject has reached the criteria for worsening asthma. Upon receipt of either of these alerts, the subject or parent/legal guardian will be instructed to call the clinic. The clinic will instruct the subject (parent/legal guardian) to provide a mucus sample for assessment of viral respiratory infection. Mucus samples for viral respiratory assessment will not be collected from subjects more than once in a 7 day period. During the randomization visit subjects will receive training on the at home collection of a mucus sample.

Throughout the study each subject will be instructed to rate their daily upper respiratory symptoms. Upper respiratory tract symptoms include: runny nose, sneezing, nasal congestion, and sore throat. Subjects will be instructed to select a rating from the following list that best describes their aggregate upper respiratory symptoms during the previous 24 hours.

This study will evaluate the effects of the ADVAIR™ DISKUS™ 100/50 mcg and FLOVENT™ DISKUS™ 100 mcg on clinical parameters and indices of airway inflammation associated with viral respiratory tract infections in pediatric asthmatic subjects. Safety will be assessed by monitoring adverse events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 339 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel Group Study of ADVAIR™ DISKUS™ 100/50 and FLOVENT™DISKUS™ 100, Both Twice Daily, in a Pediatric Population During the Fall Viral Season.
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FLOVENT™ DISKUS™ 100 mcg FLOVENT™ DISKUS™ 100 mcg is an inhaled corticosteroid indicated in the US for maintenance treatment of asthma as prophylactic therapy in patients 4 years and older.	Drug: FLOVENT™ DISKUS™ 100 mcg BID; FLOVENT™ DISKUS™ 100 mcg, one inhalation twice daily (BID) from the DISKUS device from randomization through the end of study (week 16).; Other Names: Fluticasone propionate
Experimental: ADVAIR™ DISKUS™ 100/50 mcg ADVAIR™ DISKUS™ 100/50 mcg is a combination product containing a corticosteroid and a long acting beta2 adrenergic agonist indicated for; maintenance treatment of asthma in patients 4 years of age and older.	Drug: ADVAIR™ DISKUS™ 100/50 mcg BID; ADVAIR™ DISKUS™ 100/50 mcg is a combination product containing a 100 mcg fluticasone propionate and a 50 mcg salmeterol. One inhalation from the DISKUS device twice daily (BID) from randomization through end of study (week 16).; Other Names: Fluticasone propionate/salmeterol combination

Outcome Measures

Primary Outcome Measures

1. Total Number of Asthma Exacerbations Reported During the Treatment Period [From Baseline (Week 1) until the end of treatment (up to Week 16)]

   An asthma exacerbation was defined as deterioration of asthma that required the use of outpatient oral/parenteral corticosteroids (tablets, suspensions, or injection) or an urgent care, hospitalization, or emergency room (ER) visit due to asthma that required oral/parenteral corticosteroids. Two exacerbations (out of a total of 51) were excluded: (1) one exacerbation occurred within 7 days of the resolution of an earlier one, and, per protocol, was combined with the previous exacerbation; and (2) one exacerbation occurred post treatment.

Secondary Outcome Measures

1. Mean Asthma Symptom Scores, as an Indicator of Severity, Associated With the Presence of Moderate or Severe Upper Respiratory Tract Symptoms (URTS) or a Confirmed Rhinovirus (RV) Infection at Baseline and During the Peak Viral Period [Baseline (Week 1) and Peak Viral Period ([period during which the greatest number of viral infections is expected] from 30 August 2010 through the end of the treatment period [up to Week 16])]

   Participants recorded their asthma symptom score over the previous 24 hours (during the day and the previous night) using the following 6-point scale: 0=No symptoms; 1=Symptoms for 1 short period; 2=Symptoms for >=2 short periods; 3=Symptoms for most of the day/previous night that did not affect normal daily activities; 4=Symptoms for most of the day/previous night that affected normal daily activities; 5=Symptoms so severe that participant could not perform normal daily activities. The Baseline mean asthma symptom score was calculated as the average score over 7 days prior to Week 1, Visit 2.

2. Mean Duration of Worsening Asthma Symptoms Associated With the Presence of Moderate or Severe URTS or a Confirmed RV Infection [Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])]

   A worsening asthma day is one on which any of the following occurred: rescue albuterol use above baseline, use of oral/parenteral corticosteroids for asthma, use of asthma medication other than study medication, asthma symptom scores >=3, nighttime awakenings, unscheduled health care visits, or missed school due to asthma. The duration of worsening asthma is the number of consecutive worsening asthma days after the date of a URTS score of 2 (moderate) or 3 (severe) or collection of a mucus sample containing RV (whichever occurred first). Each span of consecutive days is a participant interval.

3. Number of Asthma Exacerbations Associated With the Presence of Moderate or Severe URTS or a Confirmed RV Infection During the Peak Viral Period [Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])]

   Each participant (with assistance from the parent/legal guardian as needed) was instructed to keep an electronic diary (eDiary) with record of daily URTS symptoms that included: runny nose, sneezing, nasal congestion, and sore throat. Based on the best-described aggregate URTS during the previous 24 hours, participants rated symptoms as: 0 = Not present; 1 = Mild, clearly present; 2 = Moderately severe, uncomfortable; and 3 = Severe, interfering with sleep or activity. Mucus samples were collected and analyzed for RVwhen the eDiary alerted for moderate/severe URTS.

4. Mean Percentage of Asthma-control Days [Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])]

   An asthma-control day was defined as a day without any of the following: rescue albuterol use, use of oral/parenteral corticosteroids for asthma, use of asthma medication other than double-blind study treatment, asthma symptom score >0, nighttime awakenings due to asthma, unscheduled health care visits (defined as home visits, office visits, or urgent care visits), ER visits, hospitalizations for asthma, or school absenteeism due to asthma. The percentage of asthma-control days = the number (No.) of asthma-control days divided by the No. of days of treatment exposure, multiplied by 100.

5. Mean Percentage of Episode-free (EF) Days [Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])]

   An EF day was defined as a day without any of the following: rescue albuterol use, use of oral/parenteral corticosteroids for asthma, use of asthma medication other than study treatment, asthma symptom score >0, nighttime awakenings due to asthma, unscheduled health care visits (defined as home visits, office visits, or urgent care visits), ER visits, hospitalizations for asthma, school absenteeism due to asthma, or morning peak expiratory flow (measure of maximum airflow) <80% of baseline. Percentage of EF days=No. of EF days divided by No. of days of treatment exposure, multiplied by 100.

6. Mean Percentage of Symptom-free Days [Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])]

   A symptom-free day was defined as a day during the Peak Viral Period on which the asthma symptom score was zero. The daily asthma symptom score (measured during the day and the previous night) was reported on a 6-point scale (ranging from 0=no symptoms to 5=severe symptoms). Percentage of symptom-free days was defined as the number of days during the Peak Viral Period on which the asthma symptom score=0, divided by the number of days in that same period on which non-missing values were recorded, multiplied by 100.

7. Mean Percentage of Rescue-free Days [Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])]

   A rescue-free day was defined as a day during the Peak Viral Period on which no puffs of rescue medication were recorded. Percentage of rescue-free days was defined as the number of days during the Peak Viral Period on which no puffs of rescue medication were recorded, divided by the number of days in that same period on which non-missing values were recorded, multiplied by 100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatient

• Subjects must be between the ages of 4 and 11 at Randomization

• Subjects must attend day-care, pre-school, elementary school, or middle school. Day-care attendance is defined as receiving childcare outside the home for at least 10 hours per week. Children who are home-schooled are not eligible for this study. Children on year round and traditional school calendars are eligible for this study.

• Subjects can be randomized into this study at any time between August 2nd, 2010 and August 20th, 2010.

• Males or pre-menarchal females.

• A diagnosis of asthma, as defined by the National Institutes of Health [NIH, 2007]

• At Visit 1 subjects must demonstrate a best clinic AM PEF ≥70% of the predicted value [Polgar, 1971].

• Each subject must have a history of an exacerbation of asthma between September 1st, 2009 and May 15th, 2010 that required a burst of outpatient systemic corticosteroids (oral or parenteral on >1 days for worsening symptoms of asthma) or have had an urgent care, hospitalization, or ED visit for asthma during which they received oral/parenteral corticosteroids between September 1st, 2009 and May 15th, 2010.

• Subjects must have prior or current use of controller ICS medication as listed below:

• Subjects who have had prior use of a controller medication consisting of a low dose ICS at any time since September 1st, 2009 are eligible for inclusion in this study (refer to Table 1 for examples of allowed doses of commonly used ICS).

• Subjects currently taking a low dose ICS are eligible for inclusion in the study (refer to Table 1 for examples of allowed doses of commonly used ICS).

• Subjects' currently taking a moderate dose ICS are eligible for inclusion in the study if the subject's asthma has been controlled over the prior 3 months and the subject is a candidate for step down therapy, as defined by current asthma management guidelines [NIH, 2007].

• Subjects' currently taking low dose ICS in combination with a LABA are eligible for inclusion in the study if the subject's asthma has been controlled over the prior 3 months and the subject is a candidate for step down therapy, as defined by current asthma management guidelines [NIH, 2007].

• All subjects must be able to replace their short-acting beta2-agonists with study-issued albuterol inhalation aerosol at Visit 1 for use as needed for the duration of the study. If a subject demonstrates the inability to coordinate the use of an MDI alone, subjects are permitted to use an Aerochamber Plus spacer. The use or non-use of a spacer for albuterol inhalation aerosol should be consistent for each subject throughout the study. Subjects must be able to withhold inhaled albuterol for at least 6 hours prior to study Visits

• Chickenpox: Reported history of clinical varicella or varicella vaccine. If a subject needs varicella vaccine this will be arranged with a physician and must be received prior to randomization.

• Electronic Peak Flow Meter (ePEF)/Electronic Daily Diary (eDiary): A subject must be able to use the study-provided electronic peak flow meter and the subject/caregiver must be able to enter data using the electronic Diary record.

• Responsibilities of Consenting Parent/Legal Guardian: The subject's parent or legal guardian must commit to assist the subject at a consistent level with administration of investigational product and electronic Diary device and electronic PEF meter throughout the study.

• A subject must demonstrate adequate and appropriate technique for using the DISKUS™ device reliably.

• Fluency in English or USA Spanish: Subject and/or subject's parent/guardian must be able to read, comprehend, and record information in English or USA Spanish.

Exclusion Criteria:

• History of Life Threatening Asthma

• Unstable Asthma

• Concomitant use of corticosteroid medication

• Other Concurrent Diseases/Abnormalities: The known presence of sinus, middle ear, oropharyngeal, upper or lower respiratory tract infections within 4 weeks immediately preceding randomization that required the use of an antibiotic or was accompanied by symptoms of worsening asthma.

• Concomitant Medications: Administration of any other prescription or over the counter medication which would significantly affect the course of asthma, such as omalizumab (Xolair), or interact with sympathomimetic amines, such as: anticonvulsants (barbiturates, hydantoins, carbamazepine), polycyclic antidepressants, beta-adrenergic blocking agents (both cardio-selective and non-selective), phenothiazines,

• Cytochrome P450 3A4 (CYP 3A4) Inhibitors: A subject is not eligible if he/she is receiving a strong CYP 3A4 inhibitor within 4 weeks of Visit 1 (e.g., ritonavir, ketoconazole, itraconazole).

• Immunosuppressive medications: A subject must not be using or require use of immunosuppressive medications (e.g. methotrexate, gold, cyclosporine, azathioprine) during the study.

Note: Immunotherapy for the treatment of allergies is allowed during the study provided it was initiated 4 weeks prior to Visit 1 and the subject remains in the maintenance phase for the duration of the study.

• Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, cystic fibrosis, dyspnea by any cause other than asthma, or other respiratory abnormalities other than asthma.

• Other Concurrent Diseases/Abnormalities: Historical or current evidence of clinically significant uncontrolled disease that in the opinion of the investigator would put the safety of the subject at risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study.

The list of additional excluded conditions/diseases includes, but is not limited to the following:

Uncontrolled hypertension; Uncontrolled hematologic, hepatic, neurologic, or renal disease Uncontrolled gastroesophageal reflux disease, Immunologic compromise, Cardiac arrhythmias, Tuberculosis (current or untreated), Congestive heart failure, Cushing's disease Coronary artery disease, Addison's disease, Current malignancy, Eosinophilic esophagitis Uncontrolled diabetes mellitus, Uncontrolled thyroid disorder

• Severe Hypersensitivity to Milk Proteins: Any immediate hypersensitivity reaction, such as urticaria, angioedema, rash, and bronchospasm to milk proteins

• Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the Dry Powder Inhaler (i.e., lactose).

• Tobacco Use: A history of or present use of any tobacco products.

• Investigational Medications: A subject must not have participated in a study (including a non-interventional study) or used any investigational drug (including devices) within 30 days prior to Visit 1 or within ten half-lives (t1/2) of the prior investigational study (whichever is longer of the two).

• Child in Care: A Child in Care (CiC) is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a CiC can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The determination of whether a child meets the definition of CiC should be made with the study centre staff in consultation with the responsible IRB/Ethics Committee.

• Affiliation with Investigator's Site: A subject is an immediate family member of the participating investigator, sub investigator, study coordinator, or employee of the participating investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Tucson	Arizona	United States	85724
2	GSK Investigational Site	Bakersfield	California	United States	93301
3	GSK Investigational Site	Fresno	California	United States	93720
4	GSK Investigational Site	Granada Hills	California	United States	91344
5	GSK Investigational Site	Huntington Beach	California	United States	92647
6	GSK Investigational Site	Long Beach	California	United States	90808
7	GSK Investigational Site	Orange	California	United States	92868
8	GSK Investigational Site	Riverside	California	United States	92506
9	GSK Investigational Site	Sacramento	California	United States	95819
10	GSK Investigational Site	San Diego	California	United States	92120
11	GSK Investigational Site	Walnut Creek	California	United States	94598
12	GSK Investigational Site	Colorado Springs	Colorado	United States	80907
13	GSK Investigational Site	St. Petersburg	Florida	United States	33710
14	GSK Investigational Site	Atlanta	Georgia	United States	30342
15	GSK Investigational Site	Gainesville	Georgia	United States	30501
16	GSK Investigational Site	Lawrenceville	Georgia	United States	30045
17	GSK Investigational Site	Owensboro	Kentucky	United States	42301
18	GSK Investigational Site	Ypsilanti	Michigan	United States	48197
19	GSK Investigational Site	Brick	New Jersey	United States	08724
20	GSK Investigational Site	Albuquerque	New Mexico	United States	87131
21	GSK Investigational Site	Asheville	North Carolina	United States	28801
22	GSK Investigational Site	Canton	Ohio	United States	44718
23	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73103
24	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73112
25	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73120
26	GSK Investigational Site	Medford	Oregon	United States	97504
27	GSK Investigational Site	Collegeville	Pennsylvania	United States	19426
28	GSK Investigational Site	Orangeburg	South Carolina	United States	29118
29	GSK Investigational Site	Summerville	South Carolina	United States	29485
30	GSK Investigational Site	Boerne	Texas	United States	78006
31	GSK Investigational Site	Dallas	Texas	United States	75230
32	GSK Investigational Site	El Paso	Texas	United States	79925
33	GSK Investigational Site	Houston	Texas	United States	77054
34	GSK Investigational Site	San Antonio	Texas	United States	78229
35	GSK Investigational Site	Waco	Texas	United States	76712
36	GSK Investigational Site	Murray	Utah	United States	84107
37	GSK Investigational Site	Norfolk	Virginia	United States	23507
38	GSK Investigational Site	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Health Lung and Blood Institute Asthma Guidelines

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01192178
• Other Study ID Numbers: 113872
• First Posted: Aug 31, 2010
• Last Update Posted: Jan 18, 2017
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: pediatric; exacerbation; viral induced exacerbation; asthma
• Additional relevant MeSH terms: Asthma; Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination

Study Results

Participant Flow

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	Fluticasone Propionate/Salmeterol DISKUS Combination Product (FSC) at a dose of 100/50 micrograms (mcg) administered as one inhalation twice daily (BID) for 16 weeks	Fluticasone Propionate (FP) DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Period Title: Overall Study
STARTED	171	168
COMPLETED	147	145
NOT COMPLETED	24	23

Baseline Characteristics

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID	Total
Arm/Group Description	Fluticasone Propionate/Salmeterol DISKUS Combination Product (FSC) at a dose of 100/50 micrograms (mcg) administered as one inhalation twice daily (BID) for 16 weeks	Fluticasone Propionate (FP) DISKUS 100 mcg administered as one inhalation BID for 16 weeks	Total of all reporting groups
Overall Participants	171	168	339
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	7.5 (2.11)	7.4 (2.08)	7.4 (2.09)
Gender (Count of Participants)
Female	63 36.8%	56 33.3%	119 35.1%
Male	108 63.2%	112 66.7%	220 64.9%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	27 15.8%	33 19.6%	60 17.7%
American Indian or Alaska Native	2 1.2%	0 0%	2 0.6%
Asian	8 4.7%	6 3.6%	14 4.1%
American Indian or Alaska Native and White	1 0.6%	0 0%	1 0.3%
White	129 75.4%	127 75.6%	256 75.5%
African American/African Heritage and White	1 0.6%	1 0.6%	2 0.6%
Asian & Native Hawaiian or Other Pacific Islander	1 0.6%	0 0%	1 0.3%
Asian and White	2 1.2%	0 0%	2 0.6%
Native Hawaiian or Other Pacific Islander & White	0 0%	1 0.6%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Total Number of Asthma Exacerbations Reported During the Treatment Period
Description	An asthma exacerbation was defined as deterioration of asthma that required the use of outpatient oral/parenteral corticosteroids (tablets, suspensions, or injection) or an urgent care, hospitalization, or emergency room (ER) visit due to asthma that required oral/parenteral corticosteroids. Two exacerbations (out of a total of 51) were excluded: (1) one exacerbation occurred within 7 days of the resolution of an earlier one, and, per protocol, was combined with the previous exacerbation; and (2) one exacerbation occurred post treatment.
Time Frame	From Baseline (Week 1) until the end of treatment (up to Week 16)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants randomized to treatment. Only those participants who reported >=1 exacerbation were analyzed.

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	Fluticasone Propionate/Salmeterol DISKUS Combination Product (FSC) at a dose of 100/50 micrograms (mcg) administered as one inhalation twice daily (BID) for 16 weeks	Fluticasone Propionate (FP) DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Measure Participants	21	20
Number [Number of asthma exacerbations]	24	25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSC DISKUS 100/50 mcg BID, FP DISKUS 100 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.928
	Comments	Cox Proportional Hazards model adjusted for investigative center
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.971
	Confidence Interval	(2-Sided) 95%; 0.519 to 1.819
	Parameter Dispersion	Type: Value:
	Estimation Comments	The risk of having an asthma exacerbation during the treatment period was analyzed.

2. Secondary Outcome

Title	Mean Asthma Symptom Scores, as an Indicator of Severity, Associated With the Presence of Moderate or Severe Upper Respiratory Tract Symptoms (URTS) or a Confirmed Rhinovirus (RV) Infection at Baseline and During the Peak Viral Period
Description	Participants recorded their asthma symptom score over the previous 24 hours (during the day and the previous night) using the following 6-point scale: 0=No symptoms; 1=Symptoms for 1 short period; 2=Symptoms for >=2 short periods; 3=Symptoms for most of the day/previous night that did not affect normal daily activities; 4=Symptoms for most of the day/previous night that affected normal daily activities; 5=Symptoms so severe that participant could not perform normal daily activities. The Baseline mean asthma symptom score was calculated as the average score over 7 days prior to Week 1, Visit 2.
Time Frame	Baseline (Week 1) and Peak Viral Period ([period during which the greatest number of viral infections is expected] from 30 August 2010 through the end of the treatment period [up to Week 16])

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with moderate or severe URTS or a confirmed RV infection were analyzed.

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	FSC at a dose of 100/50 mcg administered as one inhalation BID for 16 weeks	FP DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Measure Participants	106	104
Baseline, n=105, 104	0.2 (0.41)	0.2 (0.39)
Peak Viral Period, n=106, 104	0.5 (0.84)	0.4 (0.70)

3. Secondary Outcome

Title	Mean Duration of Worsening Asthma Symptoms Associated With the Presence of Moderate or Severe URTS or a Confirmed RV Infection
Description	A worsening asthma day is one on which any of the following occurred: rescue albuterol use above baseline, use of oral/parenteral corticosteroids for asthma, use of asthma medication other than study medication, asthma symptom scores >=3, nighttime awakenings, unscheduled health care visits, or missed school due to asthma. The duration of worsening asthma is the number of consecutive worsening asthma days after the date of a URTS score of 2 (moderate) or 3 (severe) or collection of a mucus sample containing RV (whichever occurred first). Each span of consecutive days is a participant interval.
Time Frame	Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with relevant data defining a worsening asthma day during the peak viral period and with moderate or severe URTS or a confirmed RV infection were analyzed.

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	FSC at a dose of 100/50 mcg administered as one inhalation BID for 16 weeks	FP DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Measure Participants	121	145
Mean (Standard Error) [Days per participant interval]	4.1 (0.18)	4.0 (0.17)

4. Secondary Outcome

Title	Number of Asthma Exacerbations Associated With the Presence of Moderate or Severe URTS or a Confirmed RV Infection During the Peak Viral Period
Description	Each participant (with assistance from the parent/legal guardian as needed) was instructed to keep an electronic diary (eDiary) with record of daily URTS symptoms that included: runny nose, sneezing, nasal congestion, and sore throat. Based on the best-described aggregate URTS during the previous 24 hours, participants rated symptoms as: 0 = Not present; 1 = Mild, clearly present; 2 = Moderately severe, uncomfortable; and 3 = Severe, interfering with sleep or activity. Mucus samples were collected and analyzed for RVwhen the eDiary alerted for moderate/severe URTS.
Time Frame	Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who reported >=1 exacerbation were analyzed. Only those participants with moderate or severe URTS or a confirmed RV infection were analyzed.

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	FSC at a dose of 100/50 mcg administered as one inhalation BID for 16 weeks	FP DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Measure Participants	5	7
Number [Number of asthma exacerbations]	5	7

5. Secondary Outcome

Title	Mean Percentage of Asthma-control Days
Description	An asthma-control day was defined as a day without any of the following: rescue albuterol use, use of oral/parenteral corticosteroids for asthma, use of asthma medication other than double-blind study treatment, asthma symptom score >0, nighttime awakenings due to asthma, unscheduled health care visits (defined as home visits, office visits, or urgent care visits), ER visits, hospitalizations for asthma, or school absenteeism due to asthma. The percentage of asthma-control days = the number (No.) of asthma-control days divided by the No. of days of treatment exposure, multiplied by 100.
Time Frame	Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who recorded data during the Peak Viral Period, had a treatment stop date with a defined Peak Viral Period, and had available data on all days on which data were recorded were analyzed.

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	FSC at a dose of 100/50 mcg administered as one inhalation BID for 16 weeks	FP DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Measure Participants	161	156
Mean (Standard Error) [Percentage of days]	48.3 (1.51)	49.7 (1.54)

6. Secondary Outcome

Title	Mean Percentage of Episode-free (EF) Days
Description	An EF day was defined as a day without any of the following: rescue albuterol use, use of oral/parenteral corticosteroids for asthma, use of asthma medication other than study treatment, asthma symptom score >0, nighttime awakenings due to asthma, unscheduled health care visits (defined as home visits, office visits, or urgent care visits), ER visits, hospitalizations for asthma, school absenteeism due to asthma, or morning peak expiratory flow (measure of maximum airflow) <80% of baseline. Percentage of EF days=No. of EF days divided by No. of days of treatment exposure, multiplied by 100.
Time Frame	Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who recorded data during the Peak Viral Period, had a treatment stop date with a defined Peak Viral Period, and had available data on all days on which data were recorded were analyzed.

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	FSC at a dose of 100/50 mcg administered as one inhalation BID for 16 weeks	FP DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Measure Participants	161	155
Mean (Standard Error) [Percentage of days]	42.4 (1.55)	44.5 (1.61)

7. Secondary Outcome

Title	Mean Percentage of Symptom-free Days
Description	A symptom-free day was defined as a day during the Peak Viral Period on which the asthma symptom score was zero. The daily asthma symptom score (measured during the day and the previous night) was reported on a 6-point scale (ranging from 0=no symptoms to 5=severe symptoms). Percentage of symptom-free days was defined as the number of days during the Peak Viral Period on which the asthma symptom score=0, divided by the number of days in that same period on which non-missing values were recorded, multiplied by 100.
Time Frame	Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who recorded data during the Peak Viral Period and had a treatment stop date with a defined Peak Viral Period were analyzed.

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	FSC at a dose of 100/50 mcg administered as one inhalation BID for 16 weeks	FP DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Measure Participants	161	157
Mean (Standard Deviation) [Percentage of days]	90.1 (15.89)	91.1 (13.18)

8. Secondary Outcome

Title	Mean Percentage of Rescue-free Days
Description	A rescue-free day was defined as a day during the Peak Viral Period on which no puffs of rescue medication were recorded. Percentage of rescue-free days was defined as the number of days during the Peak Viral Period on which no puffs of rescue medication were recorded, divided by the number of days in that same period on which non-missing values were recorded, multiplied by 100.
Time Frame	Peak Viral Period (from 30 August 2010 through the end of treatment [up to Week 16])

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who recorded data during the Peak Viral Period and had a treatment stop date with a defined Peak Viral Period were analyzed.

Arm/Group Title	FSC DISKUS 100/50 mcg BID	FP DISKUS 100 mcg BID
Arm/Group Description	FSC at a dose of 100/50 mcg administered as one inhalation BID for 16 weeks	FP DISKUS 100 mcg administered as one inhalation BID for 16 weeks
Measure Participants	161	157
Mean (Standard Deviation) [Percentage of days]	92.1 (16.60)	91.7 (14.68)

Adverse Events

Arm/Group Title	FSC DISKUS 100/50 mcg BID		FP DISKUS 100 mcg BID
Arm/Group Description	FSC at a dose of 100/50 mcg administered as one inhalation BID for 16 weeks		FP DISKUS 100 mcg administered as one inhalation BID for 16 weeks
All Cause Mortality
	FSC DISKUS 100/50 mcg BID		FP DISKUS 100 mcg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FSC DISKUS 100/50 mcg BID		FP DISKUS 100 mcg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/171 (1.2%)		1/168 (0.6%)
Infections and infestations
Gastroenteritis	1/171 (0.6%)		0/168 (0%)
Pneumonia respiratory syncytialviral	1/171 (0.6%)		0/168 (0%)
Nervous system disorders
Syncope	0/171 (0%)		1/168 (0.6%)
Respiratory, thoracic and mediastinal disorders
Respiratory distress	1/171 (0.6%)		0/168 (0%)
Status asthmaticus	1/171 (0.6%)		0/168 (0%)
Other (Not Including Serious) Adverse Events
	FSC DISKUS 100/50 mcg BID		FP DISKUS 100 mcg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/171 (49.7%)		84/168 (50%)
General disorders
Pyrexia	20/171 (11.7%)		16/168 (9.5%)
Infections and infestations
Upper respiratory tract infection	30/171 (17.5%)		31/168 (18.5%)
Nasopharyngitis	15/171 (8.8%)		20/168 (11.9%)
Sinusitis	11/171 (6.4%)		3/168 (1.8%)
Nervous system disorders
Headache	25/171 (14.6%)		28/168 (16.7%)
Reproductive system and breast disorders
Nasal congestion	15/171 (8.8%)		13/168 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	26/171 (15.2%)		21/168 (12.5%)
Oropharyngeal pain	14/171 (8.2%)		12/168 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.