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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00441441
• Other study ID #: SFA106484
• Status: Completed
• Phase: Phase 3
• First received: February 28, 2007
• Last updated: February 26, 2015
• Start date: February 2007
• Est. completion date: January 2008

Study information

• Verified date: February 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 351
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 11 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• fluticasone propionate
fluticasone propionate 100mcg HFA
• fluticasone propionate/salmeterol
fluticasone propionate/salmeterol 100/50mcg HFA

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Clayton	Victoria
Australia	GSK Investigational Site	Parkville	Victoria
Australia	GSK Investigational Site	Subiaco	Western Australia
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Sarnia	Ontario
Canada	GSK Investigational Site	St. John's	Newfoundland and Labrador
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago
Chile	GSK Investigational Site	Viña del Mar	Valparaíso
Costa Rica	GSK Investigational Site	San Jose
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Guetersloh	Nordrhein-Westfalen
Germany	GSK Investigational Site	Kleve-Materborn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Wesel	Nordrhein-Westfalen
Latvia	GSK Investigational Site	Ogre
Latvia	GSK Investigational Site	Riga
Lithuania	GSK Investigational Site	Kaunas
Lithuania	GSK Investigational Site	Utena
Lithuania	GSK Investigational Site	Vilnius
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Mexico city
Mexico	GSK Investigational Site	Monterrey N.L	Nuevo León
Peru	GSK Investigational Site	Lima
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Rabka
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	Tomsk
Spain	GSK Investigational Site	Murcia
Spain	GSK Investigational Site	San Javier (Murcia)
United States	GSK Investigational Site	Canton	Ohio
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Cortland	New York
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Gainesville	Georgia
United States	GSK Investigational Site	Germantown	Tennessee
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Lake Oswego	Oregon
United States	GSK Investigational Site	Lakewood	Colorado
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	South Burlington	Vermont
United States	GSK Investigational Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  Costa Rica,  Germany,  Latvia,  Lithuania,  Mexico,  Peru,  Poland,  Russian Federation,  Spain, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Possible Drug-Related Adverse Events	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.	Treatment period (weeks 1-12) and Post Treatment (=1 day after last time study drug)	No
Primary	Investigator Evaluations of Electrocardiogram (ECG) Results	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.	Baseline and Week 12	No
Primary	Clinically Significant Unfavorable ECGs at Week 12	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.	Baseline, Week 12	No
Primary	ECG Measures - Heart Rate	The range of heart rates for this study was between 49-144 beats per minute	Baseline and Week 12	No
Primary	ECG Measures - QT Interval	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.	Baseline and Week 12	No
Primary	Cardiovascular Adverse Events Reported During Treatment Period	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.	12-Week Treatment Period	No
Primary	Cardiovascular Adverse Events Reported During the Post-Treatment Period	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.	5 Days after Week 12	No
Primary	Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols	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.	Treatment period (weeks 1-12)	No
Primary	Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion	"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.	Baseline and week 12	No
Primary	Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12	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.	Baseline and Week 12	No
Primary	Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion	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).	Baseline and Week 12	No
Primary	Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use	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.	Baseline and Week 12	No
Primary	Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12	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.	Baseline and Week 12	No
Primary	Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use	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).	Baseline and Week 12	No
Secondary	Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years	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.	Baseline and week 12	No
Secondary	AM Peak Expiratory Flow	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.	Baseline and 12-Week Treatment Period	No
Secondary	Asthma Symptom Scores	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.	Baseline and 12-Week Treatment Period	No
Secondary	Percentage of Symptom Free Days	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 .	Baseline and 12-Week Treatment Period	No
Secondary	Albuterol Use	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.	Baseline and 12-Week Treatment Period	No
Secondary	Percent of Albuterol-free Days	Percentage of days when Albuterol use was unnecessary based on daily record and symptom free days.	Baseline and 12-Week Treatment Period	No