A Safety and Tolerability Study of Arformoterol Tartrate Inhalation Solution in Pediatric Subjects

Study Overview
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Brief Summary
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To determine the safety and tolerability of Arformoterol Tartrate in children with asthma

Detailed Description
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A randomized, double-blind two-way crossover study of three cumulative doses of arformoterol (7.5 ug per nebulization) and levalbuterol (0.63 mg per nebulization) given over a one hour period, followed by a single open-label treatment day with three cumulative doses of arformoterol 15 ug in subjects 2-11 years of age 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 Cumulative Dose Safety and Tolerability Crossover Study of Arformoterol Tartrate Inhalation Solution and Levalbuterol Hydrochloride Inhalation Solution in Pediatric Subjects (Aged 2 to 11 Years of Age) With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: arformoterol
* Drug: levalbuterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Female Between Age 2 and 11, inclusive, at the time of consent Weight equal to or greater than 15 Kg History of physician-diagnosed asthma of at least 2 years duration for children age 6 and older, and at least 1 year duration for children 5 and younger. Exclusion Criteria: Female subject who is pregnant or lactating. Subject who has a history of hospitalization for asthma within one year, or who is scheduled for in-patient hospitalization, including elective surgery during the course of the trial. Subject with any history of life-threatening asthma defined as a history of asthma episodes requiring intubation, associated with hypercapnia, respiratory arrest, or hypoxic seizures. Subject with a history of cancer. Subject with hyperthyroidism, diabetes, hypertension, cardiac diseases or seizure disorders. Subject with a history of cigarette smoking or use of any tobacco products.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 Years

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ARF/LEV<br>Cross-over phase: one day active treatment with arformoterol 7.5 microgram per nebulization followed by a 7 day washout. Then a one day active treatment with levalbuterol 0.63 milligram per nebulization. Open-label phase: Following another 7 day washout, one day treatment with arformoterol 15 micrograms per nebulization. | Drug: arformoterol<br>* Arformoterol is given at a 7.5 ug per dosing during the cross-over phase and 15 ug per dosing during the open-label phase. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes).<br>* Other names: Brovana;Drug: levalbuterol<br>* Levalbuterol is given at a 0.63 mg per dosing during the cross-over phase. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes).<br>* Other names: Xopenex;|
| Other: LEV/ARF<br>Cross-over phase: one day active treatment with levalbuterol 0.63 milligram per nebulization followed by a 7 day washout. Then a one day active treatment with arformoterol 7.5 micrograms per nebulization. Open-label phase: Following another 7 day washout, one day treatment with arformoterol 15 micrograms per nebulization. | Drug: arformoterol<br>* Arformoterol is given at a 7.5 ug per dosing during the cross-over phase and 15 ug per dosing during the open-label phase. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes).<br>* Other names: Brovana;Drug: levalbuterol<br>* Levalbuterol is given at a 0.63 mg per dosing during the cross-over phase. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes).<br>* Other names: Xopenex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Heart Rate | Heart rate measured at various timepoints: predose and timepoints after each of the three dosings. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes). | predose, various timeframes up to 5 hours post last dose | 
| Change From Predose in Mean Heart Rate | Heart rate measured at various timepoints minus the heart rate at predose. | predose, various timeframes up to 5 hours post last dose | 
| Mean Systolic Blood Pressure | Systolic blood pressure measured at various timepoints: predose and timepoints after each of the three dosings. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes). | predose, various timeframes up to 5 hours post last dose | 
| Change From Predose in Mean Systolic Blood Pressure | Mean systolic blood pressure measured at various timepoints minus the mean systolic blood pressure at predose | predose, various timeframes up to 5 hours post last dose | 
| Mean Diastolic Blood Pressure | Diastolic blood pressure measured at various timepoints: predose and timepoints after each of the three dosings. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes). | predose, various timeframes up to 5 hours post last dose | 
| Change From Predose in Mean Diastolic Blood Pressure | Mean diastolic blood pressure measured at various timepoints minus the predose diastolic blood pressure | predose, various timeframes up to 5 hours post last dose | 
| Mean Serum Potassium Levels |  | Predose, 2 hours and 6 hours postdose 1 | 
| Change From Predose in Mean Serum Potassium | Change in mean serum potassium at the specified timepoint minus the predose value. | predose, 2 and 6 hours post dose | 
| Mean Serum Glucose Values |  | Predose, 2 and 6 hours post dose 1 | 
| Change From Predose in Mean Serum Glucose | Change in mean serum glucose at the specified timepoint minus the predose value. | predose, 2 and 6 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Forced Expiratory Volume in One Second(FEV1) | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. | predose, various postdose times | 
| Change From Predose of Mean Forced Expiratory Volume in One Second (FEV1) | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. Change in FEV1 was calculated as postdose value minus the predose value at each visit. | predose, various postdose timepoints | 
| Mean Peak Expiratory Flow Rate (PEFR) | PEFR is the fastest rate at which air can move through the airways during a forced expiration starting with fully inflated lungs as measured by peak flow meters. | predose, various postdose times | 
| Change From Predose in Mean Peak Expiratory Flow Rate (PEFR) | PEFR is the fastest rate at which air can move through the airways during a forced expiration starting with fully inflated lungs as measured by peak flow meters. Change in PEFR was calculated as postdose value minus the predose value at each visit. | predose, various postdose times | 
| Plasma Concentration of (R,R) Formoterol | If the mean plasma concentration was 'below the limit of quantification' (BLQ) which was set as <=0.5 picograms/milliliter, the value is displayed as a zero. | predose, various postdose times | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Respiratory Tract Diseases