A Safety, Efficacy and Tolerability Study in Pediatric Subjects With Asthma

A Safety, Efficacy, and Tolerability Study of Daily Dosing With Levalbuterol Tartrate HFA MDI and Placebo in Subjects Aged Birth to <48 Months With Asthma

A Safety, Efficacy, and Tolerability Study of Daily Dosing with Levalbuterol Tartrate HFA MDI and Placebo in Subjects Aged Birth to <48 Months with Asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Levalbuterol; Drug: Levalbuterol UDV TID; Drug: Placebo

Detailed Description

This is a modified-blind, randomized, placebo-controlled, multicenter, parallel-group trial of levalbuterol HFA MDI administered using a facemask and holding chamber in subjects birth to <48 months with asthma. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Allergy & Asthma Clinical Research Center
  • California
    • Cypress, California, United States, 90630
      • West Coast Clinical Trials, Llc
    • Long Beach, California, United States, 90808
      • Allergy & Asthma Care Center of Southern California
    • Orange, California, United States, 92868
      • Clinical Trials of Orange County, Inc.
    • Redwood, California, United States, 94063
      • Allergy and Asthma Consultants
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe International Research Centers
  • Florida
    • Fort Walton Beach, Florida, United States, 32547
      • All Seasons Allergy and Asthma Center, P.A.
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Brookstone Centre Parkway
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • DeKalb, Illinois, United States, 60115
      • Northern Illinois Research Associates
    • Normal, Illinois, United States, 61761
      • Sneeze, Wheeze & Itch Associates LLC
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Nassim, McMonigle, Mescia & Associates
  • Michigan
    • Grand Blanc, Michigan, United States, 48439
      • Grand Blanc Medical
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Craig A. Spiegel MD
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Midwest Allergy and Asthma center
    • Papillion, Nebraska, United States, 68046
      • The Asthma & Allergy Center, P.C.
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Utica, New York, United States, 13502
      • St. Elizabeth Health Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Dayton, Ohio, United States, 45406
      • Dayton Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Allergy, Asthma and Clinical Research Center
    • Oklahoma City, Oklahoma, United States, 73139
      • Eminence Research, LLC
  • Pennsylvania
    • Upland, Pennsylvania, United States, 19013
      • Asthma and Allergy Research Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • National Allergy, Asthma, and Uticaria Centers
    • Charleston, South Carolina, United States, 29414
      • AAC Research - PC
    • Greenville, South Carolina, United States, 29607
      • ADAC research, PA
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • The Asthma Institute, PLLC
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78759
      • Sirius Clinical Research, LLC
    • Austin, Texas, United States, 78731
      • ISIS Clinical Research, LLC
    • Boerne, Texas, United States, 78006
      • TTS Research
    • Boerne, Texas, United States, 78006
      • Hill Country Family Medical Center
    • Dallas, Texas, United States, 75230
      • Allergy/Immunology Research Center of North Texas
    • Dallas, Texas, United States, 75230
      • Dallas Allergy Immunology Research
    • El Paso, Texas, United States, 79903
      • Western Sky Medical Research
    • Katy, Texas, United States, 77450
      • Breath of Life Research Institute
    • Live Oak, Texas, United States, 78233
      • Live Oak Allergy and Asthma Clinic
    • San Antonio, Texas, United States, 78229
      • Sylvana Research Associates
    • San Antonio, Texas, United States, 78205
      • Quality Assurance Research Center, Inc.
    • San Antonio, Texas, United States, 78229
      • Southwest Allergy and Asthma, P.A.
    • Waco, Texas, United States, 76712
      • Allergy and Asthma Research Institute
    • Waco, Texas, United States, 76712
      • Allergy & Asthma Care of Waco
  • Virginia
    • Burke, Virginia, United States, 22015
      • PI-Coor Clinical Research, LLC
    • Colonial Heights, Virginia, United States, 23834
      • Colonial Heights Pediatrics
  • Washington
    • Bellingham, Washington, United States, 98225
      • Bellingham Asthma, Allergy, & Immunology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject's parent/legal guardian must give written informed consent, including privacy authorization, prior to study participation. Complete documentation regarding the consent process must be recorded in the case report form (CRF) and source documentation.
• Subject's parent/legal guardian must be willing and able to comply with the study procedures and visit schedules.
• Subject, male or female, must be between the ages of birth and <48 months, exclusive, at the time of consent.
• Subjects 24 to <48 months of age must have a history of physician-diagnosed asthma (defined as at least 3 episodes of respiratory symptoms consistent with asthma symptoms including, but not limited to, cough, wheeze, or dyspnea).
• Subjects 0 to <24 months of age must have a history of 3 episodes of respiratory symptoms that in the judgement of the investigator could be consistent with asthma or reactive airways disease.
• Subject must be in good health and not affected by any other chronic conditions, including respiratory disorders other than asthma.
• In subjects with a chest radiograph (taken 12 months prior to screening visit), no evidence of any chronic cardiopulmonary condition other than asthma should be present as discerned by the Investigator.
• Subject's parent/legal guardian must be able to complete the diary cards and medical event calendars (MEC) reliably on a daily basis and understand dosing instructions and questionnaire completion.

Exclusion Criteria:

• Subject who requires or is expected to require any disallowed medications
• Subject who has participated in an investigational drug study within 30 days prior to screening, or who is currently participating in another clinical trial.
• Subject or parent/legal guardian who has daily commitments during the study that would interfere with trial measurements, compliance, or both.
• Subject who has a history of hospitalization for asthma, reactive airways disease, or bronchospasm within 4 weeks prior to screening or who is scheduled for in-patient hospitalization, including elective surgery during the course of the trial.
• Subject who has experienced significant blood loss within 60 days of study drug.
• Subject with a clinical diagnosis of cystic fibrosis.
• Subject who was born prematurely, defined as less than 38 weeks gestational age at birth, and is <1 year of age at screening
• Subject whose body weight is less than 7.0 kg at screening. This minimum weight requirement is based upon standard pediatric growth charts [CDC 2000].
• Subject with a known sensitivity to levalbuterol or racemic albuterol, or any of the excipients contained in any of these formulations.
• Subject using any prescription drug with which levalbuterol or racemic albuterol sulfate administration is contraindicated.
• Subject with a history of life-threatening asthma, defined as previous asthma episodes requiring intubation or associated with hypercapnia, respiratory arrest, or hypoxic seizures.
• Subject with clinically significant abnormalities that may interfere with the metabolism or excretion of the study drugs or study participation (eg, abnormalities of renal, hepatic, metabolic, or endocrine function).
• Subject with a history of cancer.
• Subject with any chronic or congenital cardiorespiratory condition other than asthma including, but not limited to, bronchopulmonary dysplasia, congenital heart disease, and cystic fibrosis.
• Subject affected by an upper or lower respiratory tract infection in the 3 weeks prior to screening.
• Subject with a history of ventilation for a respiratory condition occurring at or near birth, including those associated with prematurity or bronchopulmonary dysplasia. Ventilatory support for elective non-cardiopulmonary surgery is not exclusionary. - Subject with any clinically significant abnormal laboratory values (hematology, blood chemistry).
• Subject with a clinically significant abnormal 12-lead ECG that would put the subject at risk for experiencing adverse cardiac effects.
• Subject who is a relative of a staff member.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 3; Placebo	Drug: Placebo; Placebo (2 actuations)
Experimental: 1; 90 ug Levalbuterol (2 actuations)	Drug: Levalbuterol; 90 ug Levalbuterol (2 actuations); Other Names: Xopenex HFA Inhalation Aerosol
Active Comparator: 2; 0.31 ug Levalbuterol UDV TID	Drug: Levalbuterol UDV TID; 0.31 ug Levalbuterol UDV TID; Other Names: Xopenex Inhalation Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Visit 4 in the Mean Daily Composite Score Based on the Pediatric Asthma Caregiver Assessments (PACA)	The daily composite score is the sum of the scores of 5 domains: Nocturnal Awakenings Due to Wheeze and Cough, Daytime Wheeze, Daytime Cough, Shortness of Breath, and Asthma Symptom Score. A possible score of 0 (no symptoms) to 19 (severe symptoms). The mean daily composite score at Visit 4 is defined as the mean of the daily composite scores in the week prior to Visit 4.	Baseline, Visit 4 (Week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Visit 3 in Mean Daily Composite Score Based on the Pediatric Asthma Caregiver Assessment	The daily composite score is the sum of the scores of 5 domains: Nocturnal Awakenings Due to Wheeze and Cough, Daytime Wheeze, Daytime Cough, Shortness of Breath, and Asthma Symptom Score. A possible score of 0 (no symptoms) to 19 (severe symptoms). The mean daily composite score at Visit 3 is defined as the mean of the daily composite scores in the 7 days prior to Visit 3.	Baseline, Visit 3 (Week 3)
Change From Baseline to Visit 2 to Visit 3 in the Mean Daily Composite Score Based on the Pediatric Asthma Caregiver Assessment	The daily composite score is the sum of the scores of 5 domains: Nocturnal Awakenings Due to Wheeze and Cough, Daytime Wheeze, Daytime Cough, Shortness of Breath, and Asthma Symptom Score. A possible score of 0 (no symptoms) to 19 (severe symptoms). The mean daily composite score from Visit 2 to Visit 3 is defined as the mean of the daily composite scores from Visit 2 (inclusive) to the day prior to Visit 3.	The days from Visit 2 (inclusive) to the day prior to Visit 3 - approximately 14 days
Change From Baseline to Visit 3 to Visit 4 in the Mean Daily Composite Score Based on the Pediatric Asthma Caregiver Assessment	The daily composite score is the sum of the scores of 5 domains: Nocturnal Awakenings Due to Wheeze and Cough, Daytime Wheeze, Daytime Cough, Shortness of Breath, and Asthma Symptom Score. A possible score of 0 (no symptoms) to 19 (severe symptoms). The mean daily composite score from Visit 3 to Visit 4 is defined as the mean of the daily composite scores from Visit 3 (inclusive) to the day prior to Visit 4.	The days from Visit 3 (inclusive) to the day prior to Visit 4 - approximately 14 days
Change From Baseline to Visit 3 in the Mean Daily Composite Score Based on the Daytime and Nighttime Asthma Symptom Scores as Measured by the Pediatric Asthma Questionnaire (PAQ)	The daily composite score is the sum of the scores of 7 items: Difficulty Breathing, Cough, Wheeze, Activity Limitation, Level of Activity Limitation, Overall Symptom Score, and Nighttime Asthma. The range for the PAQ is 0 (no symptoms) to 27 (severe symptoms). The mean daily composite score at Visit 3 is defined as the mean daily composite scores for 7 days prior to Visit 3.	Baseline, Visit 3 (Week 3)
Change From Baseline to Visit 4 in the Mean Daily Composite Score Based on the Daytime and Nighttime Asthma Symptom Scores as Measured by Pediatric Asthma Questionnaire	The daily composite score is the sum of the scores of 7 items: Difficulty Breathing, Cough, Wheeze, Activity Limitation, Level of Activity Limitation, Overall Symptom Score, and Nighttime Asthma. The range for the PAQ is 0 (no symptoms) to 27 (severe symptoms). The mean daily composite score at Visit 4 is defined as the mean daily composite scores in the 7 days prior to Visit 4.	Baseline, Visit 4 (Week 4)
Change From Baseline to Visit 2 to Visit 3 in the Mean Daily Composite Score Based on the Daytime and Nighttime Asthma Symptom Scores as Measured by the Pediatric Asthma Questionnaire	The daily composite score is the sum of the scores of 7 items: Difficulty Breathing, Cough, Wheeze, Activity Limitation, Level of Activity Limitation, Overall Symptom Score, and Nighttime Asthma. The range for the PAQ is 0 (no symptoms) to 27 (severe symptoms). The mean daily composite score from Visit 2 to Visit 3 is defined as the mean of the daily composite scores from Visit 2 (inclusive) to the day prior to Visit 3.	The days from Visit 2 (inclusive) to the day prior to Visit 3 - approximately 14 days
Change From Baseline to Visit 3 to Visit 4 in the Mean Daily Composite Score Based on the Daytime and Nighttime Asthma Symptom Score as Measured by the Pediatric Asthma Questionnaire	The daily composite score is the sum of the scores of 7 items: Difficulty Breathing, Cough, Wheeze, Activity Limitation, Level of Activity Limitation, Overall Symptom Score, and Nighttime Asthma. The range for the PAQ is 0 (no symptoms) to 27 (severe symptoms). The mean daily composite score from Visit 3 to Visit 4 is defined as the mean of the daily composite scores from Visit 3 (inclusive) to the day prior to Visit 4.	The days from Visit 3 (inclusive) to the day prior to Visit 4 - approximately 14 days
Change From Baseline in In-Clinic Peak Expiratory Flow to Postdose Timepoints at Visit 2	Peak expiratory flow (PEF) measures how fast a person can breathe out using the greatest effort	Baseline, Visit 2: 30 minutes post-dose (on the day of randomization), 1 hour post-dose, 4 hours post-dose, 6 hours post-dose
Change From Baseline in In-Clinic Peak Expiratory Flow to Postdose Timepoint at Visit 3		Baseline, Visit 3, pre-dose (approximately 14 days after randomization)
Change From Baseline in In-Clinic Peak Expiratory Flow to Postdose Timepoint at Visit 4		Visit 4: pre-dose (approximately 28 days after randomization) , 30 minutes post-dose, 1 hour post-dose, 4 hours post-dose, 6 hours post-dose
Percent Change From Baseline in In-Clinic Peak Expiratory Flow to Postdose Timepoints at Visit 2		Baseline, Visit 2: , 30 minutes post-dose (on the day of randomization), 1 hour post-dose, 4 hours post-dose, 6 hours post-dose
Percent Change From Baseline in In-Clinic Peak Expiratory Flow to Postdose Timepoints at Visit 3		Baseline, Visit 3, pre -dose (approximately 14 days after randomization)
Percent Change From Baseline in In-Clinic Peak Expiratory Flow to Postdose Timepoints at Visit 4		Baseline, Visit 4, pre -dose (approximately 28 days after randomization)
Change From Baseline in the At-Home Mean Daily Peak Expiratory Flow (PEF to Postdose Timepoint at Visit 3 and Visit 4	Mean of the daily pre-dose PEF values in the week prior to visit in those subjects aged 24 to <48 months capable of performing acceptable and reproducible PEF maneuvers.	Baseline, Visit 3 (the week prior to Visit 3) and Visit 4
Percent Change From Baseline in the At-Home Mean Daily Peak Expiratory Flow (PEF to Postdose Timepoint at Visit 3 and Visit 4)	Mean of the daily pre-dose PEF values in the week prior to visit in those subjects aged 24 to <48 months capable of performing acceptable and reproducible PEF maneuvers.	Visit 3 (the week prior to Visit 3), Visit 4 (the week prior to Visit 4)
Investigator Global Assessment - Question 1	Since the start of the study, how would you evaluate the child's asthma symptoms?	Visit 4 (End of 28 day treatment period)
Investigator Global Assessment - Question 2	Since the start of the study, how would you evaluate your ability to manage the subject's asthma?	Visit 4 (End of 28 day treatment period)
Caregiver Global Assessment - Question 1	Since the start of the study, how would you evaluate your child's asthma symptoms?	Visit 4 (End of 28 day treatment period)
Caregiver Global Assessment - Question 2	Since the start of the study, how would you evaluate your ability to manage your child's asthma?	Visit 4 (End of 28 day treatment period)
Caregiver Global Assessment - Question 3	Overall I was: Very satisfied with the control of the child's asthma symptoms while enrolled in this study, Moderately satisfied with the control of the child's asthma symptoms while enrolled in this study, Slightly satisfied with the control of the child's asthma symptoms while enrolled in this study, Not satisfied with the control of the child's asthma symptoms while enrolled in this study or answer Missing	Visit 4 (End of 28 day treatment period)
Rescue Medication Use: Number of Subjects Using Rescue Medication During the Treatment Period	Number of subjects using rescue medication during the treatment period	Visit 2 to Visit 3 (the first 2 weeks of the study) , Visit 3 to Visit 4 (the second 2 weeks of the study), Visit 2 to Visit 4 (the entire 4 weeks of the study)
Rescue Medication Use - Change From Baseline in Mean Number of Days Used Per Week When Used		Visit 2 to Visit 3 (the first 2 weeks of the study) , Visit 3 to Visit 4 (the second 2 weeks of the study), Visit 2 to Visit 4 (the entire 4 weeks of the study)
Rescue Medication Use - Change From Baseline in Mean Number of Doses Used Per Week		Visit 2 to Visit 3 (the first 2 weeks of the study) , Visit 3 to Visit 4 (the second 2 weeks of the study), Visit 2 to Visit 4 (the entire 4 weeks of the study)
Rescue Medication Use - Change From Baseline in Mean Number of Doses Used Per Week During Weeks When Used		Visit 2 to Visit 3 (the first 2 weeks of the study), Visit 3 to Visit 4 (the second 2 weeks of the study), Visit 2 to Visit 4 (the entire 4 weeks of the study)
Change From Baseline to Visit 3 and Visit 4 in the Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLA) Composite Score	The PACQLQ composite score was calculated as the mean of the scores of the 13 individual questions. Composite scores could range from 1 to 7. Lower scores indicated greater impact of disease on quality of life.	Visit 3 and Visit 4 (End of 28 day treatment period)

Collaborators and Investigators

• Sponsor: Sunovion

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: December 15, 2008
• First Submitted That Met QC Criteria: December 16, 2008
• First Posted (Estimate): December 17, 2008

Study Record Updates

• Last Update Posted (Estimate): July 28, 2014
• Last Update Submitted That Met QC Criteria: July 1, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: 051-359