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

• ClinicalTrials.gov Identifier: NCT00583947
• Recruitment Status: Completed
• First Posted: January 2, 2008
• Results First Posted: February 8, 2010
• Last Update Posted: February 22, 2012
• Sponsor: Sunovion
• Information provided by (Responsible Party): Sunovion

Study Description

Brief Summary:

To determine the safety and tolerability of Arformoterol Tartrate in children with asthma

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: arformoterol; Drug: levalbuterol	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: January 2008
• Actual Primary Completion Date: December 2008
• Actual Study Completion Date: December 2008

Arms and Interventions

Arm	Intervention/treatment
ARF/LEV; 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; 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).; Other Name: Brovana; Drug: levalbuterol; 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).; Other Name: Xopenex
LEV/ARF; 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; 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).; Other Name: Brovana; Drug: levalbuterol; 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).; Other Name: Xopenex

Outcome Measures

Primary Outcome Measures :

1. Mean Heart Rate [ Time Frame: predose, various timeframes up to 5 hours post last dose ]
   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).
2. Change From Predose in Mean Heart Rate [ Time Frame: predose, various timeframes up to 5 hours post last dose ]
   Heart rate measured at various timepoints minus the heart rate at predose.
3. Mean Systolic Blood Pressure [ Time Frame: predose, various timeframes up to 5 hours post last dose ]
   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).
4. Change From Predose in Mean Systolic Blood Pressure [ Time Frame: predose, various timeframes up to 5 hours post last dose ]
   Mean systolic blood pressure measured at various timepoints minus the mean systolic blood pressure at predose
5. Mean Diastolic Blood Pressure [ Time Frame: predose, various timeframes up to 5 hours post last dose ]
   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).
6. Change From Predose in Mean Diastolic Blood Pressure [ Time Frame: predose, various timeframes up to 5 hours post last dose ]
   Mean diastolic blood pressure measured at various timepoints minus the predose diastolic blood pressure
7. Mean Serum Potassium Levels [ Time Frame: Predose, 2 hours and 6 hours postdose 1 ]
8. Change From Predose in Mean Serum Potassium [ Time Frame: predose, 2 and 6 hours post dose ]
   Change in mean serum potassium at the specified timepoint minus the predose value.
9. Mean Serum Glucose Values [ Time Frame: Predose, 2 and 6 hours post dose 1 ]
10. Change From Predose in Mean Serum Glucose [ Time Frame: predose, 2 and 6 hours post dose ]
    Change in mean serum glucose at the specified timepoint minus the predose value.

Secondary Outcome Measures :

1. Mean Forced Expiratory Volume in One Second(FEV1) [ Time Frame: predose, various postdose times ]
   Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer.
2. Change From Predose of Mean Forced Expiratory Volume in One Second (FEV1) [ Time Frame: predose, various postdose timepoints ]
   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.
3. Mean Peak Expiratory Flow Rate (PEFR) [ Time Frame: predose, various postdose times ]
   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.
4. Change From Predose in Mean Peak Expiratory Flow Rate (PEFR) [ Time Frame: predose, various postdose times ]
   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.
5. Plasma Concentration of (R,R) Formoterol [ Time Frame: predose, various postdose times ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 11 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Beverly Hills, California, United States, 90211

Orange, California, United States, 92868

United States, Georgia

Savannah, Georgia, United States, 31406

United States, Illinois

Normal, Illinois, United States, 61761

United States, Oklahoma

Oklahoma City, Oklahoma, United States, 73112

Oklahoma City, Oklahoma, United States, 73120

United States, Oregon

Medford, Oregon, United States, 97504

Portland, Oregon, United States, 97213

United States, Pennsylvania

Upland, Pennsylvania, United States, 19013

United States, South Carolina

Orangeburg, South Carolina, United States, 29118

Spartanburg, South Carolina, United States, 29303

United States, Texas

Dallas, Texas, United States, 75230

United States, Virginia

Burke, Virginia, United States, 22015

Richmond, Virginia, United States, 23229

Sponsors and Collaborators

Sunovion

Investigators

• Study Chair: Pulmonary Medical Director; Unicorn Pharma Consulting

More Information

Additional Information:

Brovana Patient Medication Guide 

Publications of Results:

Hinkle J, Hinson J, Kerwin E, Goodwin E, Sciarappa K, Curry L, Hanrahan JP. A cumulative dose, safety and tolerability study of arformoterol in pediatric subjects with stable asthma. Pediatr Pulmonol. 2011 Aug;46(8):761-9. doi: 10.1002/ppul.21446. Epub 2011 May 16.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT00583947
• Other Study ID Numbers: 091-029
• First Posted: January 2, 2008
• Results First Posted: February 8, 2010
• Last Update Posted: February 22, 2012
• Last Verified: January 2012

Keywords provided by Sunovion:

Asthma; Respiratory Tract Diseases

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Albuterol; Formoterol Fumarate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Tocolytic Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action