Trial Outcomes & Findings for Treatment Of Symptomatic Asthma In Children (NCT NCT00197106)

Results Overview

Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

176 participants

Primary outcome timeframe

Last 10 weeks of the treatment period (Weeks 16-26)

Results posted on

2017-03-14

Participant Flow

Participants were eligible to enter the run-in period if they had a documented clinical history of asthma with hyperresponsiveness. Only participants who were symptomatic after this period were eligible to be enrolled into the study and were randomized into either the Salmeterol/Fluticasone propionate (FP) 50/100 mcg plus placebo or FP groups.

257 participants started the run-in phase of the study, and 99 of these did not meet the inclusion criteria to be entered into the treatment phase. Only baseline characteristics for the 158 participants meeting the inclusion criteria and randomized to either salmeterol/fluticasone propionate 50/100 mcg BID or fluticasone 200 mcg BID are provided.

Participant milestones

Participant milestones
Measure	Fluticasone Propionate (FP) 100 mcg Fluticasone propionate (FP) 100 mcg (micrograms) twice daily (BID) via DISKUS inhaler	Salmeterol/FP 50/100 mcg Plus Placebo One puff Salmeterol/FP 50/100 mcg plus one puff placebo (matching one puff of FP in the 200 mcg group) BID via DISKUS inhaler	FP 200 mcg FP 200 mcg (delivered as two 100 mcg puffs) BID via DISKUS inhaler
4-Week Run-In Period STARTED	257	0	0
4-Week Run-In Period COMPLETED	158	0	0
4-Week Run-In Period NOT COMPLETED	99	0	0
Overall Treatment Period STARTED	0	78	80
Overall Treatment Period COMPLETED	0	77	74
Overall Treatment Period NOT COMPLETED	0	1	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Fluticasone Propionate (FP) 100 mcg Fluticasone propionate (FP) 100 mcg (micrograms) twice daily (BID) via DISKUS inhaler	Salmeterol/FP 50/100 mcg Plus Placebo One puff Salmeterol/FP 50/100 mcg plus one puff placebo (matching one puff of FP in the 200 mcg group) BID via DISKUS inhaler	FP 200 mcg FP 200 mcg (delivered as two 100 mcg puffs) BID via DISKUS inhaler
4-Week Run-In Period Did not meet entry criteria	99	0	0
Overall Treatment Period Lack of Efficacy	0	1	0
Overall Treatment Period Lost to Follow-up	0	0	2
Overall Treatment Period Protocol Violation	0	0	2
Overall Treatment Period Withdrawal by Subject	0	0	2

Baseline Characteristics

Treatment Of Symptomatic Asthma In Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=78 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=80 Participants FP 200 mcg BID via DISKUS inhaler	Total n=158 Participants Total of all reporting groups
Age, Continuous	9.4 years STANDARD_DEVIATION 1.8 • n=5 Participants	9.3 years STANDARD_DEVIATION 1.9 • n=7 Participants	9.3 years STANDARD_DEVIATION 1.8 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	31 Participants n=7 Participants	67 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	49 Participants n=7 Participants	91 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	73 participants n=5 Participants	75 participants n=7 Participants	148 participants n=5 Participants
Race/Ethnicity, Customized Mixed	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized African-American	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized African	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Asthma duration	5.7 years STANDARD_DEVIATION 3.1 • n=5 Participants	5.5 years STANDARD_DEVIATION 3.0 • n=7 Participants	5.6 years STANDARD_DEVIATION 3.0 • n=5 Participants

PRIMARY outcome

Timeframe: Last 10 weeks of the treatment period (Weeks 16-26)

Population: Per protocol (PP) population: participants of the Intent-to-Treat (ITT) Population (participants who had taken at least one dose of study medication) who completed the study without any major protocol violations

Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary.

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=73 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=76 Participants FP 200 mcg BID via DISKUS inhaler
Percentage of Symptom-free Days During the Last 10 Weeks of the Treatment Period	50.45 percentage of days Standard Deviation 33.52	49.75 percentage of days Standard Deviation 35.77

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: Per protocol (PP) population: participants of the Intent-to-Treat (ITT) Population (participants who had taken at least one dose of study medication) who completed the study without any major protocol violations

Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=73 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=76 Participants FP 200 mcg BID via DISKUS inhaler
Percentage of Symptom-free Days During the Entire Treatment Period Baseline	22.78 percentage of days Standard Deviation 25.30	23.06 percentage of days Standard Deviation 25.23
Percentage of Symptom-free Days During the Entire Treatment Period 0-6 weeks	31.58 percentage of days Standard Deviation 31.34	31.50 percentage of days Standard Deviation 29.73
Percentage of Symptom-free Days During the Entire Treatment Period 6-16 weeks	44.60 percentage of days Standard Deviation 34.67	45.24 percentage of days Standard Deviation 34.58
Percentage of Symptom-free Days During the Entire Treatment Period 16-26 weeks	50.45 percentage of days Standard Deviation 33.52	49.75 percentage of days Standard Deviation 35.77

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Per protocol (PP) population: participants of the Intent-to-Treat (ITT) Population (participants who had taken at least one dose of study medication) who completed the study without any major protocol violations. At baseline there were 6 missing data and 4 improper testings that could not be used in the analysis.

Change from Baseline was calculated as the Week 26 value minus the Baseline value. The percentage predicted FEV1 is defined as the volume of air that can be forced out in one second after taking a deep breath and is corrected for the FEV1 value corresponding with the same age.

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=61 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=61 Participants FP 200 mcg BID via DISKUS inhaler
Mean Change From Baseline in Percentage Predicted Forced Expiratory Volume in One Second (FEV1) at Week 26	102.5 percent predicted change Standard Deviation 14.2	103.0 percent predicted change Standard Deviation 15.3

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Per protocol (PP) population: participants of the Intent-to-Treat (ITT) Population (participants who had taken at least one dose of study medication) who completed the study without any major protocol violations. At baseline there were 6 missing data and 4 improper testings that could not be used in the analysis.

Change from Baseline was calculated as the Week 26 value minus the Baseline value. Forced vital capacity is defined as the maximum volume of air that can be forcibly expired from the lungs and is calculated by use of spirometry. The spirometry test is performed by using a device called a spirometer, which measures the amount of air one can blow out maximally. Generally, the participant is asked to take the deepest breath they can, and then exhale into the sensor as hard as possible, for as long as possible. The test is normally repeated three times to ensure reproducibility.

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=61 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=61 Participants FP 200 mcg BID via DISKUS inhaler
Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 26	2.28 liters Standard Deviation 0.62	2.28 liters Standard Deviation 0.59

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Per protocol (PP) population: participants of the Intent-to-Treat (ITT) Population (participants who had taken at least one dose of study medication) who completed the study without any major protocol violations. For some participants, the data for the MEF 50 measurements are missing, resulting in a smaller number of participants analyzed.

Change from Baseline was calculated as the Week 26 value minus the Baseline value. MEF 50 is defined as maximum expiratory flow rate at 50% of vital capacity. Vital capacity is the maximum amount of air that a person can expel from the lungs after first filling the lungs to their maximum extent. Midexpiratory flow was calculated by use of spirometry. The test is normally repeated at least three times in order to ensure reproducibility.

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=57 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=57 Participants FP 200 mcg BID via DISKUS inhaler
Mean Change From Baseline in Midexpiratory Flow (MEF 50) at Week 26	2.28 liters/second Standard Deviation 0.67	2.19 liters/second Standard Deviation 0.72

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Per protocol (PP) population: participants of the Intent-to-Treat (ITT) Population (participants who had taken at least one dose of study medication) who completed the study without any major protocol violations and completed two NO measurements (Baseline and Week 26)

Geometric mean values of NO at week 26 were compared using ANCOVA with adjustment for baseline value of NO, age, gender and center. Analysis of covariance (ANCOVA) is a general linear model with one continuous outcome variable (quantitative) and one or more factor variables.

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=27 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=31 Participants FP 200 mcg BID via DISKUS inhaler
Geometric Means of Nitric Oxide (NO) at Week 26	8.6 parts per billion Interval 1.9 to 64.0	10.0 parts per billion Interval 1.8 to 51.6

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: PP Population: Intent-to-Treat (ITT) Population participants who completed the study without any major protocol violations and completed two NO measurements (Baseline and Week 26). For some participants, the data for the RINT measurement are missing, either at Baseline or at Week 26. As a result, fewer subjects have been included in the analysis.

Change from Baseline was calculated as the Week 26 value minus the Baseline value. Interrupter respiratory resistance (RINT) measurements were calculated by a combined analysis for relation between change from baseline and occurrence of the endpoint. RINT is a technique that is used for evaluating lung function in poorly collaborating patients (e.g., small children). The measurement is performed during tidal breathing (normal breathing) instead of during maximal expiration, as is done by a spirometry test.

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=57 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=57 Participants FP 200 mcg BID via DISKUS inhaler
Percent Change From Baseline in RINT Measurements at Week 26	-9.1 percent	-9.9 percent

SECONDARY outcome

Timeframe: Week 26

Population: Intent-to-Treat (ITT) Population (participants who had taken at least one dose of study medication)

An exacerbation is defined as a worsening of the asthma complaints (commonly referred to as an asthma attack) and is reported by the participant experiencing the event. An exacerbation was verified by the use of asthma rescue medication.

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=80 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=78 Participants FP 200 mcg BID via DISKUS inhaler
Number of Asthma Exacerbations Per Treatment Group at Week 26	10 number of exacerbations	7 number of exacerbations

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Per protocol (PP) population: participants of the Intent-to-Treat (ITT) Population (participants who had taken at least one dose of study medication) who completed the study without any major protocol violations. From this population, only participants who had measurements at both baseline and Week 26 have been used for analysis.

PD20 was calculated by using increasing dosages of methacholine. The dosage that caused a 20% fall in FEV1 was used for analysis. The presented data are ratios (month 6/Baseline) of geometric mean PD20 values.

Outcome measures

Outcome measures
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=65 Participants Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=61 Participants FP 200 mcg BID via DISKUS inhaler
Mean Change From Baseline in Provocation Dose (PD20) Causing a 20% Fall in FEV1 at Week 26	2.7 ratio Interval 1.05 to 6.7	1.5 ratio Interval 0.7 to 2.9

Adverse Events

Salmeterol/FP 50/100 mcg Plus Placebo

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

FP 200 mcg

Serious events: 3 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=78 participants at risk Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=80 participants at risk FP 200 mcg BID via DISKUS inhaler
Respiratory, thoracic and mediastinal disorders Worsening of asthma	2.6% 2/78	0.00% 0/80
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.00% 0/78	1.2% 1/80
Musculoskeletal and connective tissue disorders Reactive arthritis	0.00% 0/78	1.2% 1/80
Musculoskeletal and connective tissue disorders Bone cyst	0.00% 0/78	1.2% 1/80

Other adverse events

Other adverse events
Measure	Salmeterol/FP 50/100 mcg Plus Placebo n=78 participants at risk Salmeterol/FP 50/100 mcg plus placebo BID via DISKUS inhaler	FP 200 mcg n=80 participants at risk FP 200 mcg BID via DISKUS inhaler
Respiratory, thoracic and mediastinal disorders Common cold	35.9% 28/78	21.2% 17/80
Nervous system disorders Headache	17.9% 14/78	26.2% 21/80
Respiratory, thoracic and mediastinal disorders Sore throat	10.3% 8/78	7.5% 6/80

Additional Information

GSK Response Center

GlaxoSmithKline

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

Restriction type: OTHER