Trial Outcomes & Findings for Seretide Versus Flixotide In Asthmatic Children Not Controlled By Inhaled Corticosteroids (NCT NCT00353873)

NCT ID: NCT00353873

Last Updated: 2018-05-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

506 participants

Primary outcome timeframe

Baseline; Week 1 up to Week 12

Results posted on

2018-05-29

Participant Flow

The study was conducted at 46 sites in 12 countries: Belgium (4), Denmark (1), France (8), Italy (3), Latvia (3), Lithuania (3), the Netherlands (6), Norway (1), Poland (4), Russian Federation (9), Spain (3) and Sweden (1) from 18 November 2005 to 26 October 2006.

A total of 584 participants were screened and entered into a 4-week run-in period receiving fluticasone propionate (FP) 100 microgram (mcg) dry powder inhaler (DISKUS) twice-daily (BD) and inhaled salbutamol as required. The number of participants randomized was 321 and 303 participants received investigational product post randomization.

Participant milestones

Participant milestones
Measure
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.
Salmeterol/Fluticasone Propionate (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.
Overall Study
STARTED
153
150
Overall Study
COMPLETED
147
147
Overall Study
NOT COMPLETED
6
3

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
Salmeterol/Fluticasone Propionate (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.
Overall Study
Protocol Violation
1
2
Overall Study
Exacerbation
1
0
Overall Study
Adverse Event
1
0
Overall Study
Physician Decision
2
0
Overall Study
Withdrawal by Subject
1
1

Baseline Characteristics

Seretide Versus Flixotide In Asthmatic Children Not Controlled By Inhaled Corticosteroids

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
FP 200 mcg BD
n=153 Participants
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.
SFC 50/100 mcg BD
n=150 Participants
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.
Total
n=303 Participants
Total of all reporting groups
Age, Continuous
8.0 Years
STANDARD_DEVIATION 2.01 • n=99 Participants
8.1 Years
STANDARD_DEVIATION 2.00 • n=107 Participants
8.0 Years
STANDARD_DEVIATION 2.00 • n=206 Participants
Sex: Female, Male
Female
55 Participants
n=99 Participants
53 Participants
n=107 Participants
108 Participants
n=206 Participants
Sex: Female, Male
Male
98 Participants
n=99 Participants
97 Participants
n=107 Participants
195 Participants
n=206 Participants
Race/Ethnicity, Customized
African American/African Heritage
3 Participants
n=99 Participants
2 Participants
n=107 Participants
5 Participants
n=206 Participants
Race/Ethnicity, Customized
White - Arabic/North African Heritage
4 Participants
n=99 Participants
4 Participants
n=107 Participants
8 Participants
n=206 Participants
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
146 Participants
n=99 Participants
144 Participants
n=107 Participants
290 Participants
n=206 Participants

PRIMARY outcome

Timeframe: Baseline; Week 1 up to Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
FP 200 mcg BD
n=152 Participants
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.
SFC 50/100 mcg BD
n=150 Participants
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.
Mean Change From Baseline in Morning Peak Expiratory Flow (PEF) Over 12 Weeks in Intent-to-treat (ITT) Population
19.3 Liters/Minute (L/min)
Standard Error 2.12
26.9 Liters/Minute (L/min)
Standard Error 2.13

PRIMARY outcome

Timeframe: Baseline; Week 1 up to Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
FP 200 mcg BD
n=135 Participants
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.
SFC 50/100 mcg BD
n=127 Participants
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.
Mean Change From Baseline in Morning PEF Over 12 Weeks in Per Protocol (PP) Population
18.4 L/min
Standard Error 2.14
27.7 L/min
Standard Error 2.21

SECONDARY outcome

Timeframe: Week 5 up to Week 12

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

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.

Outcome measures

Outcome measures
Measure
FP 200 mcg BD
n=152 Participants
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.
SFC 50/100 mcg BD
n=150 Participants
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.
Number of Participants Who Achieved 'Totally Controlled' (TC) Asthma
23 Participants
28 Participants

SECONDARY outcome

Timeframe: Week 5 up to Week 12

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

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.

Outcome measures

Outcome measures
Measure
FP 200 mcg BD
n=152 Participants
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.
SFC 50/100 mcg BD
n=150 Participants
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.
Number of Participants Who Achieved WC Asthma
61 Participants
65 Participants

Adverse Events

FP 200 mcg BD

Serious events: 3 serious events
Other events: 61 other events
Deaths: 0 deaths

SFC 50/100 mcg BD

Serious events: 3 serious events
Other events: 55 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
FP 200 mcg BD
n=153 participants at risk
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.
SFC 50/100 mcg BD
n=150 participants at risk
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.
Injury, poisoning and procedural complications
Concussion
0.00%
0/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
0.67%
1/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Respiratory, thoracic and mediastinal disorders
Asthma
0.65%
1/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
0.67%
1/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Gastrointestinal disorders
Gastritis
0.65%
1/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
0.00%
0/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Infections and infestations
Laryngotracheitis
0.00%
0/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
0.67%
1/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Infections and infestations
Wound infection
0.65%
1/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
0.00%
0/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.

Other adverse events

Other adverse events
Measure
FP 200 mcg BD
n=153 participants at risk
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.
SFC 50/100 mcg BD
n=150 participants at risk
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.
Infections and infestations
Nasopharyngitis
12.4%
19/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
9.3%
14/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Infections and infestations
Rhinitis
6.5%
10/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
8.0%
12/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Respiratory, thoracic and mediastinal disorders
Cough
6.5%
10/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
4.7%
7/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
6.5%
10/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
4.0%
6/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Nervous system disorders
Headache
15.0%
23/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
18.0%
27/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
Gastrointestinal disorders
Abdominal pain
3.9%
6/153 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.
5.3%
8/150 • Serious adverse events and non-serious adverse events were collected from the first day of treatment until the last day of treatment (up to 12 weeks).
On-treatment serious adverse events and non-serious adverse events were reported for ITT Population.

Additional Information

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Phone: 866-435-7343

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

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