Treatment Of Symptomatic Asthma In Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00197106
First received: September 9, 2005
Last updated: May 31, 2012
Last verified: April 2012
  Purpose

This study is being conducted to investigate whether in childhood salmeterol/ fluticasone propionate 50/100 bd delivered via the Diskus® inhaler and fluticasone propionate 200 mcg bd delivered via the Diskus® inhaler are non- inferior in terms of symptom control. Additionally we aim to show that salmeterol/ fluticasone propionate 50/100 bd is at least as good in terms of lung function improvement and bronchial hyperreactivity and enables a steroid-sparing management of asthma in children.


Condition Intervention Phase
Asthma
Drug: Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
Drug: fluticasone propionate 2 x 100 mcg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: See Detailed Description

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Percentage of Symptom-free Days During the Last 10 Weeks of the Treatment Period [ Time Frame: Last 10 weeks of the treatment period (Weeks 16-26) ] [ Designated as safety issue: No ]
    Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary.


Secondary Outcome Measures:
  • Percentage of Symptom-free Days During the Entire Treatment Period [ Time Frame: Baseline to Week 26 ] [ Designated as safety issue: No ]
    Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary

  • Mean Change From Baseline in Percentage Predicted Forced Expiratory Volume in One Second (FEV1) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Midexpiratory Flow (MEF 50) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    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.

  • Geometric Means of Nitric Oxide (NO) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in RINT Measurements at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    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.

  • Number of Asthma Exacerbations Per Treatment Group at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Provocation Dose (PD20) Causing a 20% Fall in FEV1 at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    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.

  • Bronchial Hyperresponsiveness With PD20 AMP in Selected Centres [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Bronchial hyperresponsiveness with PD20 AMP in selected centres was not analyzed, as this outcome measure was removed in a protocol amendment.

  • Daily FEV1 and PEF Via the Electronic Peak Flow/FEV1 Meter (PIKO-1) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Daily FEV1 and PEF via the electronic pea kflow/FEV1 meter (PIKO-1) was not assessed because data from the peak flow meters could not be used for analysis.

  • Frequency of Asthma Exacerbations (Discriminated on Severity) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    The frequency of asthma exacerbations (discriminated on severity) was not analyzed because of the low overall frequency.

  • Cumulative Number of Symptom-free Weeks Until the End of Treatment [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.

  • Weekly Percentage of Participants With 'Good Controlled Weeks' and 'Maximal Controlled Weeks' [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.

  • Time to Asthma Control, Defined as the Time to First 'Good Controlled Week' or 'Maximum Controlled Week' [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.


Enrollment: 176
Study Start Date: June 2005
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: arm 1
Active Comparator single arm study
Drug: Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
comparator
Drug: fluticasone propionate 2 x 100 mcg
comparator
Other Names:
  • Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
  • fluticasone propionate 2 x 100 mcg

Detailed Description:

A multicentre, randomised, double blind, parallel group study to compare the efficacy and safety of Salmeterol/Fluticasone propionate combination product (Seretide®) 50/100mcg with Fluticasone propionate (Flixotide®) 200mcg, both delivered twice daily via the DISKUS inhaler, in the treatment of children aged 6-12 years with symptomatic asthma.

  Eligibility

Ages Eligible for Study:   6 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Male or female subjects aged 6-12 years (inclusive)
  • A female is eligible to enter and participate in the study if she is:

of non-child-bearing potential; OR of child-bearing potential, but not lactating and pregnant. She declares that it is not probable that she will become pregnant during the study (a pregnancy test can be performed at the investigators discretion)

  • Subjects with a documented history of asthma for at least 6 months
  • Subjects with a documented history of BHR within 12 months prior to inclusion or BHR on visit 1 (PD20 methacholine < 150 mcg or an equivalence for histamine)
  • Subjects who have received BDP, budesonide up to 100-200 mcg bd or fluticasone propionate at a dose of up to 125 mcg bd for at least 4 weeks before the start of the run-in period.
  • Subjects who are able to use a electronic peakflow /FEV1 meter (PIKO-1)
  • Subjects who have a normal length SD score between -2SD and +2SD
  • Subjects who are able to use a Diskus inhaler
  • Subjects who are able to perform reproducible lung function tests at visit 1 (variation FEV1 < 5% between the two best measurements)
  • Subjects and their guardians, who have given written informed consent to participate in the study
  • Subjects or their parent/ guardian who are able to understand and complete a DRC. The DRC may be completed by a parent/guardian if the subject is unable to do this him/ herself
  • Subjects able to use Ventolin on an 'as required for symptoms' basis

Exclusion criteria:

  • Subjects who have been hospitalised for their asthma within 4 weeks of visit 1
  • Subjects who had an acute upper respiratory tract infection within 2 weeks or a lower respiratory tract infection within 4 weeks prior to visit 1
  • Subjects who received oral, parental or depot corticosteroids within 4 weeks prior to visit 1
  • Subjects who have a known respiratory disorder other than asthma and/or systemic/thoracic abnormalities which influence normal lung function
  • Subjects with a disorder that affects growth (e.g. Turner's syndrome)
  • Subjects who have received any investigational drugs within 4 weeks of visit 1
  • Subjects with a known or suspected hypersensitivity to inhaled steroids, β2-agonists or lactose
  • Subjects who use any medication that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazole
  • Subjects who concurrently participate in another clinical study
  • Subjects who have previously been randomised in this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00197106

Locations
Netherlands
GSK Investigational Site
Almere, Netherlands, 1315 RA
GSK Investigational Site
Amsterdam, Netherlands, 1105 AZ
GSK Investigational Site
Arnhem, Netherlands, 6815 AD
GSK Investigational Site
Breda, Netherlands, 4819 EV
GSK Investigational Site
Den Haag, Netherlands, 2566 MJ
GSK Investigational Site
Eindhoven, Netherlands, 5623 EJ
GSK Investigational Site
Enschede, Netherlands, 7511JX
GSK Investigational Site
Gouda, Netherlands, 2803 HG
GSK Investigational Site
Groningen, Netherlands, 9713 GZ
GSK Investigational Site
Helmond, Netherlands, 5707 HA
GSK Investigational Site
Hoorn, Netherlands, 1624 NP
GSK Investigational Site
Leeuwarden, Netherlands, 8934 AD
GSK Investigational Site
Maastricht, Netherlands, 6229 HX
GSK Investigational Site
Nijmegen, Netherlands, 6532 SZ
GSK Investigational Site
Sittard, Netherlands, 6131 BK
GSK Investigational Site
Utrecht, Netherlands, 3584 CX
GSK Investigational Site
Veldhoven, Netherlands, 5504 DB
GSK Investigational Site
Zwolle, Netherlands, 8025 AB
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00197106     History of Changes
Other Study ID Numbers: SAM101667
Study First Received: September 9, 2005
Results First Received: September 11, 2009
Last Updated: May 31, 2012
Health Authority: Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by GlaxoSmithKline:
salmeterol/fluticasone combination
Asthma
bronchial hyperresponsiveness
Children
symptom control

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Salmeterol
Fluticasone
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 22, 2014