A 12-Week Study To Assess The Safety Of Fluticasone Propionate/Salmeterol 100/50 HFA Versus Fluticasone Propionate 100 HFA In Children With Asthma

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00441441
First received: February 28, 2007
Last updated: August 30, 2010
Last verified: August 2010
  Purpose

This study is to assess the safety of an investigational drug in children 4 to 11 years of age who have asthma. The subjects will attend 7 clinic visits, of which up to 3 will be in the morning, and have lung function tests performed.


Condition Intervention Phase
Asthma
Drug: fluticasone propionate 100mcg HFA
Drug: fluticasone propionate/salmeterol 100/50mcg HFA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel Group Study Evaluating the Safety of Fluticasone Propionate/Salmeterol 100/50mcg HFA (2 Inhalations of 50/25mcg) Twice Daily Compared With Fluticasone Propionate 100mcg HFA (2 Inhalations of 50mcg) Twice Daily in Subjects 4-11 Years of Age With Persistent Asthma

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Possible Drug-Related Adverse Events [ Time Frame: Treatment period (weeks 1-12) and Post Treatment (≥1 day after last time study drug) ] [ Designated as safety issue: No ]
    Adverse Events reported by the Investigator and judged by the Investigator to be possibly related to study drug, categorized by the Medical Dictionary for Regulatory Activities (MeDRA), were reported. ECG, electrocardiogram. QTc and QT represent intervals on an ECG.

  • Investigator Evaluations of Electrocardiogram (ECG) Results [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    ECGs were transmitted to an independent cardiologist who was responsible for providing interpretation of the ECG as either normal or abnormal (based on personal assessment). The investigator was then responsible for determining the clinical significance of the abnormal ECG in the context of the participants' history and clinical presentation. An abnormal, clinically significant ECG included, but was not limited to: prolonged QT interval, ischemic changes, ventricular hypertrophy, intraventricular conduction abnormalities, and clinically significant arrhythmias. PD, premature discontinuation.

  • Clinically Significant Unfavorable ECGs at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Post-randomization ECGs categorized by the primary investigator as no change, significant change (favorable), significant change (unfavorable) from the ECG performed at Visit 1 (Baseline) are presented. Significant change (favorable) includes any ECG that improved from baseline, whereas significant change (unfavorable) includes any ECG that worsened from baseline. Clinical significance is determined by the primary investigator.

  • ECG Measures - Heart Rate [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The range of heart rates for this study was between 49-144 beats per minute

  • ECG Measures - QT Interval [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Fridericia's formula QTc interval=QT interval/cubed root of the R-R interval. The Bazett's formula QTc=QT/squared root of the R-R interval.

  • Cardiovascular Adverse Events Reported During Treatment Period [ Time Frame: 12-Week Treatment Period ] [ Designated as safety issue: No ]
    Cardiovascular Adverse Events, as categorized by the Medical Dictionary for Regulatory Activities (MeDRA), reported during Treatment Period.

  • Cardiovascular Adverse Events Reported During the Post-Treatment Period [ Time Frame: 5 Days after Week 12 ] [ Designated as safety issue: No ]
    Cardiovascular Adverse Events, as categorized by the Medical Dictionary for Regulatory Activities (MeDRA), reported during Post-treatment period, defined as 1 day after last dose of study drug

  • Asthma Exacerbations [ Time Frame: Treatment period (weeks 1-12) ] [ Designated as safety issue: No ]
    Summary of the number of participants who reported Asthma Exacerbations

  • Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    Normal range for Cortisol levels vary by age and gender

  • Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Normal range for Cortisol levels vary by age and gender. Geometric mean is the product of the values taken to the Nth root, where N is the number of values in the set of values.

  • Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Normal range for Cortisol levels vary by age and gender. The data provided are a direct calculation of the Week 12 geometric mean divided by the baseline value.

  • Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of a Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask.

  • Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. Geometric mean is the product of the values taken to the Nth root, where N is the number of values in the set of values.

  • Geometric Mean Ratio for Week12:Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. The data provided are a direct calculation of the Week 12 geometric mean divided by the baseline value.


Secondary Outcome Measures:
  • Clinic AM Forced Expiratory Volume in Participants 6-11 Years [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    FEV1 (Forced Expiratory Volume in 1 second) is the volume of air that can be forced out in one second, after taking a deep breath. FEV1 is measured using a spirometer and obtaining "best effort" from 3 to 8 measurements. Week 12 is the measure taken at Week 12.

  • AM Peak Expiratory Flow [ Time Frame: Baseline and 12-Week Treatment Period ] [ Designated as safety issue: No ]
    The peak expiratory flow (PEF) rate measures how fast a person can exhale air. It is used to compare to normal flow rates to predict obstruction and disease. The average PEF for a child or adolescent whose height is 43" is 147 L/min, whose height is 66" is 454 L/min. Triplicate measurements taken for the best effort recorded.

  • Asthma Symptom Scores [ Time Frame: Baseline and 12-Week Treatment Period ] [ Designated as safety issue: No ]
    Each morning prior to dosing or PEF, self-scored based on past 24 hours: 0=No symptoms, 1=Symptoms for one short period, 2=Symptoms for two or more short periods, 3=Frequent Symptoms that did not affect Activities of daily living(ADL), 4=Frequent symptoms that did affect ADL, 5=Symptoms so severe that subject could not go to school or perform ADL.

  • Percentage of Symptom Free Days [ Time Frame: Baseline and 12-Week Treatment Period ] [ Designated as safety issue: No ]
    Percentage of number of days without asthma symptoms based on Asthma Symptom Scores. Each morning prior to dosing or PEF, asthma symptoms were self-scored based on the past 24 hours: 0=no symptoms, 1=symptoms for one short period, 2=symptoms for two or more short periods, 3=frequent symptoms that did not affect activities of daily living (ADL), 4=frequent .

  • Albuterol Use [ Time Frame: Baseline and 12-Week Treatment Period ] [ Designated as safety issue: No ]
    Albuterol inhalation aerosol was used as a rescue or prophylactic and recorded daily by subject or caregiver. The number of puffs of albuterol over the previous 24 hour period prior to dosing was recorded.

  • Percent of Albuterol-free Days [ Time Frame: Baseline and 12-Week Treatment Period ] [ Designated as safety issue: No ]
    Percentage of days when Albuterol use was unnecessary based on daily record and symptom free days.


Enrollment: 300
Study Start Date: February 2007
Intervention Details:
    Drug: fluticasone propionate 100mcg HFA Drug: fluticasone propionate/salmeterol 100/50mcg HFA
    Other Names:
    • fluticasone propionate 100mcg HFA
    • fluticasone propionate/salmeterol 100/50mcg HFA
  Eligibility

Ages Eligible for Study:   4 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Must have asthma.
  • Must be currently taking an inhaled corticosteroid.
  • Must be able to attend 7 clinic visits, of which up to 3 will be in the morning, and have lung function tests that are at least 60% of normal (AM FEV1 or PEF).
  • Have a historical or current FEV1 or PEF reversibility of >=12%.

Exclusion criteria:

  • Has ever had life-threatening asthma (for example respiratory arrest, mechanical ventilation).
  • Has a current ear or respiratory tract infection.
  • Has ever had any other major illnesses (such as cystic fibrosis, heart problems, tuberculosis).
  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: NCT00441441

  Show 65 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

Publications:
Li JS, Qaqundah PY, Weinstein SF, LaForce CF, Ellsworth AV, Ortega HG, Ferro TJ. Fluticasone propionate/salmeterol combination in children with asthma: key cardiac and overall safety results. Clin Res Reg Affairs 2010;27(3):87-95.

ClinicalTrials.gov Identifier: NCT00441441     History of Changes
Other Study ID Numbers: SFA106484
Study First Received: February 28, 2007
Results First Received: January 23, 2009
Last Updated: August 30, 2010
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
asthma
fluticasone propionate
children
fluticasone propionate/salmeterol

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

ClinicalTrials.gov processed this record on September 22, 2014