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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: Levalbuterol
* Drug: Levalbuterol UDV TID
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 48 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>90 ug Levalbuterol (2 actuations) | Drug: Levalbuterol<br>* 90 ug Levalbuterol (2 actuations)<br>* Other names: Xopenex HFA Inhalation Aerosol;|
| Active Comparator: 2<br>0.31 ug Levalbuterol UDV TID | Drug: Levalbuterol UDV TID<br>* 0.31 ug Levalbuterol UDV TID<br>* Other names: Xopenex Inhalation Solution;|
| Placebo Comparator: 3<br>Placebo | Drug: Placebo<br>* Placebo (2 actuations)<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma