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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00441441
First received: February 28, 2007
Last updated: February 26, 2015
Last verified: February 2015
  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
Drug: fluticasone propionate/salmeterol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
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 (corrected QT interval) 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. The Adverse Events were identified in any ECG interpretation by a central reader (Cardiologist) for any ECG obtained after the first treatment dose and were then reported by the Primary Investigator as an Adverse Event. Please see the category titles for a list of candidate cardiovascular adverse events.

  • 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. The Adverse Events were identified in any ECG interpretation by a central reader (Cardiologist) for any ECG obtained after the first treatment dose and were then reported by the Primary Investigator as an Adverse Event.

  • Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols [ Time Frame: Treatment period (weeks 1-12) ] [ Designated as safety issue: No ]
    The Primary Investigator determined the severity of the exacerbation based on the participant's clinical presentation and the investigator's understanding of the disease, the participant, and his or her clinical experiences. The severity of the exacerbation was not defined in the protocol. Mild: Usually treated at home. Prompt relief with inhaled short-acting beta2 agonist. Possible short course of oral systemic corticosteroids. Moderate: Usually requires office or emergency department visit. Relief with frequent inhaled short-acting beta2 agonist. Oral systemic corticosteroids; some symptoms last for 1-2 days after treatment begins. Severe: Usually requires emergency department visit and likely hospitalization. Partial relief with frequent inhaled short-acting beta2 agonist. Oral systemic corticosteroids; some symptoms last for more than 3 days after treatment begins. Adjunctive therapies are helpful.

  • Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    "Abnormal high cortisol excretion" and "Abnormal low cortisol excretion" are defined as above the upper limit of normal and below the lower limit of normal, respectively. The normal range for cortisol levels vary by age and gender. An abnormality is defined as a value of 24-hour urinary cortisol excretion that is outside the normal range. The normal range for 24-hour urinary cortisol excretion was provided by the central laboratory.

  • 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, nanomoles per 24 hours (nmol/24 hrs).

  • 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 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. "Abnormal high cortisol excretion" and "Abnormal low cortisol excretion" are defined as above the upper limit of normal and below the lower limit of normal, respectively. An abnormality is defined as a value of 24-hour urinary cortisol excretion that is outside the normal range. The normal range for 24-hour urinary cortisol excretion was provided by the central laboratory.

  • 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, nanomoles per 24 hours (nmol/24 hrs).


Secondary Outcome Measures:
  • Clinic Morning (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 inches is 147 Liters/minute (L/min), whose height is 66 inches 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 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 which did not affect activities of daily living (ADL), 4=Frequent.

  • 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: 351
Study Start Date: February 2007
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fluticasone propionate/salmeterol 100/50 HFA
Fluticasone propionate/salmeterol 100/50 HFA (2 inhalations of 50/25mcg), twice daily (strengths are ex-valve) and a placebo HFA inhaler matching the fluticasone propionate 100mcg HFA inhaler (2 inhalations) twice daily
Drug: fluticasone propionate/salmeterol
fluticasone propionate/salmeterol 100/50mcg HFA
Experimental: Fluticasone propionate 100mcg HFA
Fluticasone propionate 100mcg HFA (2 inhalations of 50mcg), twice daily (strengths are ex-valve) and a placebo HFA inhaler matching the fluticasone propionate/salmeterol 100/50 HFA inhaler (2 inhalations ) twice daily
Drug: fluticasone propionate
fluticasone propionate 100mcg 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 55 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials 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.

Responsible Party: GlaxoSmithKline
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: February 26, 2015
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on July 26, 2015