Seretide Versus Flixotide In Asthmatic Children Not Contr... | NCT00353873

NCT00353873

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Fluticasone propionate (FLIXOTIDE™)	Active Comparator	Fluticasone propionate (FLIXOTIDE™) at a dose of 200μg twice daily	Drug: Fluticasone propionate
Fluticasone propionate/salmeterol (SERETIDE™)	Experimental	Salmeterol/fluticasone propionate combination (SERETIDE™) at a dose of 50/100μg twice daily	Drug: Fluticasone propionate/salmeterol

Name	Type	Description	Arm Group Labels	Other Names
Fluticasone propionate	Drug	200μg twice daily	Fluticasone propionate (FLIXOTIDE™)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in Morning Peak Expiratory Flow (PEF) Over 12 Weeks in Intent-to-treat (ITT) Population	PEF is the maximum flow generated during expiration, as measured with a peak flow meter and recorded in electronic diary record card (eDRC), performed with maximal force and started after a full inspiration. The mean morning PEF measurement was constructed by calculating a simple mean for each participant over the interval Weeks 1 to 12. All PEF measurements were converted to the Wright/McKerow peak flow meter scale for the purposes of analyses. The change from Baseline is then calculated by subtracting the Baseline PEF values from the individual on-treatment values. Baseline was calculated as the mean of the values recorded on the seven days preceding randomization. The analysis was done using analysis of covariance (ANCOVA) adjusted for baseline PEF, country amalgamation, age, sex and treatment.	Baseline; Week 1 up to Week 12
Mean Change From Baseline in Morning PEF Over 12 Weeks in Per Protocol (PP) Population	PEF is the maximum flow generated during expiration, as measured with a peak flow meter and recorded in eDRC, performed with maximal force and started after a full inspiration. The mean morning PEF measurement was constructed by calculating a simple mean for each participant over the interval Weeks 1 to 12. All PEF measurements were converted to the Wright/McKerow peak flow meter scale for the purposes of analyses. The change from Baseline is then calculated by subtracting the Baseline PEF values from the individual on-treatment values. Baseline was calculated as the mean of the values recorded on the seven days preceding randomization. The analysis was done using ANCOVA adjusted for baseline PEF, country amalgamation, age, sex and treatment.	Baseline; Week 1 up to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Who Achieved 'Totally Controlled' (TC) Asthma	TC asthma is defined as no daily symptoms, no night-time wakening due to asthma, no exacerbations, no rescue salbutamol/albuterol use, no emergency visits, >=80% predicted morning PEF, and no treatment related adverse events enforcing a change in asthma therapy over 7 consecutive days. Number of participants/group who achieved the status of at least TC during the last 8 weeks (wks) of treatment was analyzed using logistic regression, including covariates for sex, age, treatment group, country amalgamation and baseline pre-bronchodilator Forced Expiratory Volume in one second (FEV1). Asthma control was assessed each week for the last 8 wks of treatment period. Each week was classified as 'TC', 'Well Controlled' (WC), 'Not Controlled' or 'Unevaluable'. A participant was considered to have TC asthma if they achieved 4/4, 5/5, 6/6, 6/7, 7/8 or 8/8 wks that were TC. 'Unevaluable' classification included participants with less than 4 wks of data during the assessment period.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

A documented clinical history of asthma for a period of at least 6 months.
A documented history (within 12 months of Visit 1) of airway reversibility of = 15% based either on Forced expiratory volume (FEV1) or PEF measured pre and post inhalation of 200 mcg salbutamol. (If no documented history of reversibility exists, patients must demonstrate a =15% reversibility at Visit 1).
Receiving an inhaled corticosteroid at a medium dose (beclomethasone dipropionate HydroFluoroAlkane (HFA) non fine particle = 400-500 mcg/day or beclomethasone HFA fine particle = 200mcg/day, or budesonide =400 mcg/day or fluticasone = 200 mcg/day (or fluticasone 250mcg/day if subject is taking a 125mcg MDI rather than the 100mcg Diskus), for at least 3 months prior to Visit 1 and at a stable dose for at least 4 weeks prior to Visit 1.
Able to use the Mini-Wright peak flow meter and subject or parent/guardian had to be able to record the subject's maximum PEF correctly.
Able to perform FEV1 correctly.
Subject's guardian/parent able to complete an eDRC on behalf of the subject. The eDRC should be completed by the guardian/parent.
Able to use a DISKUS™ correctly.
At least one parent(s)/guardian(s) has to give written informed consent to participate in the study.

At the end of the run-in period (Visit 2), subjects must still meet the criteria for entry into the run-in period and also have:

not achieved the criteria for the 'Well-controlled' asthma during two or more of the 4 weeks prior to Visit 2.

Exclusion criteria:

Female subjects who have reached menarche.
Received any investigational study medication in the 4 weeks prior to Visit 1.
Experienced a respiratory tract infection in the 4 weeks prior to Visit 1.
Experienced an acute asthma exacerbation requiring emergency room treatment within 4 weeks or hospitalisation within 12 weeks of Visit 1.
Any use of oral/parenteral or depot corticosteroid within 12 weeks of Visit 1.
Any use of long-acting inhaled beta2-agonists or oral beta2-agonists within 4 weeks of Visit 1.
Any use of leukotriene antagonists or theophyllines within 4 weeks of Visit 1.
Any known clinical or laboratory evidence of a serious uncontrolled disease (including serious psychological disorders) which is, in the opinion of the investigator, likely to interfere with the study.
Subjects with a known or suspected hypersensitivity to inhaled corticosteroids, beta2-agonists, or any components of the formulations (e.g. lactose)
A relative of any of the site staff, including the investigator or study co-coordinator.
Has previously been entered into this study.

Subjects will be excluded from participating in the treatment period of the study if the following occurred during the run-in period:

Pre-bronchodilator FEV1 <60% (assuming that measurement was correctly performed).
Any change in asthma medication (excluding use of prophylactic study specific salbutamol for prevention of asthma symptoms due to exercise).
Respiratory tract infection or asthma exacerbation.
Use of oral, parenteral or depot corticosteroids.
Emergency visit due to asthma.
Non-compliance with the completion of the eDRC (i.e. during the 4 week period between visits, non compliance is defined as less than 5 days of completed data within any one week for four weeks - subjects must complete at least 5 days a week for the entire run-in period).

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Bruges		8000	Belgium
GSK Investigational Site

References Module

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
SAM104926	Individual Participant Data Set	View IPD

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	FP 200 mcg BD	Participants received one inhalation from dry powder inhaler A (FP 100 mcg) and dry powder inhaler B (FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation metered dose inhaler (MDI) to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	FP 200 mcg BD	Participants received one inhalation from dry powder inhaler A (FP 100 mcg) and dry powder inhaler B (FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation MDI to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.
BG001	SFC 50/100 mcg BD	Participants received one inhalation from dry powder inhaler A (SFC 50/100 mcg) and dry powder inhaler B (placebo for FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation MDI to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG0008.0± 2.01 BG0018.1± 2.00 BG0028.0± 2.00

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00055 BG00153 BG002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

African American/African Heritage

Title	Measurements
	BG0003 BG0012 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Change From Baseline in Morning Peak Expiratory Flow (PEF) Over 12 Weeks in Intent-to-treat (ITT) Population

PEF is the maximum flow generated during expiration, as measured with a peak flow meter and recorded in electronic diary record card (eDRC), performed with maximal force and started after a full inspiration. The mean morning PEF measurement was constructed by calculating a simple mean for each participant over the interval Weeks 1 to 12. All PEF measurements were converted to the Wright/McKerow peak flow meter scale for the purposes of analyses. The change from Baseline is then calculated by subtracting the Baseline PEF values from the individual on-treatment values. Baseline was calculated as the mean of the values recorded on the seven days preceding randomization. The analysis was done using analysis of covariance (ANCOVA) adjusted for baseline PEF, country amalgamation, age, sex and treatment.

ITT Population: All participants randomized to treatment who received at least one dose of randomized study medication. Only participants with analyzable data at the indicated time point were assessed.

Posted

Least Squares Mean

Standard Error

Liters/Minute (L/min)

Baseline; Week 1 up to Week 12

ID	Title	Description
OG000	FP 200 mcg BD	Participants received one inhalation from dry powder inhaler A (FP 100 mcg) and dry powder inhaler B (FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation MDI to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.
OG001	SFC 50/100 mcg BD	Participants received one inhalation from dry powder inhaler A (SFC 50/100 mcg) and dry powder inhaler B (placebo for FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation MDI to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.

Units	Counts
Participants	OG000152 OG001150

Title

Denominators

Categories

Title	Measurements
	OG00019.3± 2.12 OG00126.9± 2.13

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.012		Mean Difference (Net)	7.6	Standard Error of the Mean	3.01	2-Sided	95	1.7	13.5					Non-Inferiority or Equivalence	Non-inferiority was tested using a one-sided significance level of 2.5%. If the lower confidence interval for the difference SFC-FP falls above -12 L/min the once daily SFC treatment combination was deemed to be statistically non-inferior. In the event that the lower confidence limit (2.5% 1-sided significance) exceeded 0, and using a separate closed testing procedure, superiority could be established.

Primary

Mean Change From Baseline in Morning PEF Over 12 Weeks in Per Protocol (PP) Population

PEF is the maximum flow generated during expiration, as measured with a peak flow meter and recorded in eDRC, performed with maximal force and started after a full inspiration. The mean morning PEF measurement was constructed by calculating a simple mean for each participant over the interval Weeks 1 to 12. All PEF measurements were converted to the Wright/McKerow peak flow meter scale for the purposes of analyses. The change from Baseline is then calculated by subtracting the Baseline PEF values from the individual on-treatment values. Baseline was calculated as the mean of the values recorded on the seven days preceding randomization. The analysis was done using ANCOVA adjusted for baseline PEF, country amalgamation, age, sex and treatment.

PP Population: All participants in the ITT Population who did not have any protocol violations which could impact treatment effect. Only participants with analyzable data at the indicated time point were assessed.

Posted

Least Squares Mean

Standard Error

L/min

Baseline; Week 1 up to Week 12

ID	Title	Description
OG000	FP 200 mcg BD	Participants received one inhalation from dry powder inhaler A (FP 100 mcg) and dry powder inhaler B (FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation MDI to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.
OG001	SFC 50/100 mcg BD

Secondary

Number of Participants Who Achieved 'Totally Controlled' (TC) Asthma

TC asthma is defined as no daily symptoms, no night-time wakening due to asthma, no exacerbations, no rescue salbutamol/albuterol use, no emergency visits, >=80% predicted morning PEF, and no treatment related adverse events enforcing a change in asthma therapy over 7 consecutive days. Number of participants/group who achieved the status of at least TC during the last 8 weeks (wks) of treatment was analyzed using logistic regression, including covariates for sex, age, treatment group, country amalgamation and baseline pre-bronchodilator Forced Expiratory Volume in one second (FEV1). Asthma control was assessed each week for the last 8 wks of treatment period. Each week was classified as 'TC', 'Well Controlled' (WC), 'Not Controlled' or 'Unevaluable'. A participant was considered to have TC asthma if they achieved 4/4, 5/5, 6/6, 6/7, 7/8 or 8/8 wks that were TC. 'Unevaluable' classification included participants with less than 4 wks of data during the assessment period.

ITT Population. Only participants with analyzable data at the indicated time point were assessed.

Posted

Number

Participants

Week 5 up to Week 12

ID	Title	Description
OG000	FP 200 mcg BD	Participants received one inhalation from dry powder inhaler A (FP 100 mcg) and dry powder inhaler B (FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation MDI to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.
OG001

Secondary

Number of Participants Who Achieved WC Asthma

WC asthma is defined as two or more of symptom score >1 only allowed on <=2 days/week, rescue salbutamol/albuterol use on <=2 days/week and up to a maximum of 4 times per week, >=80% predicted morning PEF daily assessed for 7 consecutive days and all the following criteria: no night-time awakening due to asthma, no exacerbations, no emergency visits, no treatment related adverse events enforcing a change in any asthma therapy. Number of participants/group who achieved the status of at least WC during the last 8 wks of treatment was analyzed using logistic regression, including covariates for sex, age, treatment group, country amalgamation and baseline prebronchodilator FEV1. Each week was classified as 'WC', 'Not Controlled' or 'Unevaluable'. A participant was considered to have WC asthma if they achieved 4/4, 5/5, 6/6, 6/7, 7/8 or 8/8 wks that were WC. 'Unevaluable' classification included participants with less than 4 wks of data during the assessment period.

ITT Population. Only participants with analyzable data at the indicated time point were assessed.

Posted

Number

Participants

Week 5 up to Week 12

ID	Title	Description
OG000	FP 200 mcg BD	Participants received one inhalation from dry powder inhaler A (FP 100 mcg) and dry powder inhaler B (FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation MDI to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.
OG001

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FP 200 mcg BD	Participants received one inhalation from dry powder inhaler A (FP 100 mcg) and dry powder inhaler B (FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation metered dose inhaler (MDI) to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.			3	153	61	153
EG001	SFC 50/100 mcg BD	Participants received one inhalation from dry powder inhaler A (SFC 50/100 mcg) and dry powder inhaler B (placebo for FP 100 mcg) BD, in the morning and evening for 12 weeks. Participants were provided salbutamol 100 mcg per actuation MDI to be used as needed throughout the study, for prevention of exercise induced asthma and symptomatic relief from asthma symptoms.			3	150	55	150

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Concussion	Injury, poisoning and procedural complications	MedDRA 9.1	Systematic Assessment	EG0000 affected153 at risk EG0011 affected150 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 9.1	Systematic Assessment	EG0001 affected153 at risk EG0011 affected150 at risk
Gastritis	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0001 affected153 at risk EG0010 affected150 at risk
Laryngotracheitis	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG0000 affected153 at risk EG0011 affected150 at risk
Wound infection	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG0001 affected153 at risk EG0010 affected150 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 9.1	Systematic Assessment	EG00010 affected153 at risk EG0017 affected150 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 9.1	Systematic Assessment	EG00010 affected153 at risk EG0016 affected150 at risk
Headache	Nervous system disorders	MedDRA 9.1	Systematic Assessment	EG00023 affected153 at risk EG00127 affected150 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0006 affected153 at risk EG0018 affected150 at risk
Nasopharyngitis	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG00019 affected153 at risk EG00114 affected150 at risk
Rhinitis	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG00010 affected153 at risk EG00112 affected150 at risk

ID	Term
D001249	Asthma

Ancestor Terms

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Term
D000068298	Fluticasone
D000068297	Fluticasone-Salmeterol Drug Combination

Ancestor Terms

ID	Term
D000730	Androstadienes
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D000068299	Salmeterol Xinafoate
D000420	Albuterol
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines
D010627	Phenethylamines
D005021	Ethylamines
D004338	Drug Combinations
D004364	Pharmaceutical Preparations