A Pilot Study to Determine the Most Effective Dose of Arformoterol for Treating Acute Asthmatic Patients

A Pilot Study to Determine the Most Effective Dose of Arformoterol for Treating Acute Asthmatic Patients Presenting to the Emergency Department and to Evaluate Its Side Effect and Safety Profile When Used in This Clinical Situation.

The purpose of this study is to determine the best dose of nebulized arformoterol, a quick onset but long acting beta agonist, for use in treating acute bronchospasm in asthmatics presenting to the the Emergency Department. Also this study will evaluate the side effect and safety profile of arformoterol when used in this situation.

Study Overview

• Status: Terminated
• Conditions: Acute Asthma
• Intervention / Treatment: Drug: arformoterol (RR formoterol); Drug: placebo; Drug: levalbuterol

Detailed Description

Acute bronchospasm associated with exacerbations of asthma is a common problem. Currently the mainstay of treatment is inhalation albuterol, either levalbuterol or racemic mixture, in repetitive fashion depending on the resolution of the airways obstruction. Formoterol is a long-acting (>12 hours) selective beta2-agonist that has a very rapid onset of bronchodilatation (<3 minutes and thus similar to that produced by albuterol). Patients with acute bronchospasm could benefit from the prn use of formoterol as they would receive acute relief of their symptoms and this would last for a prolonged time period. Additionally formoterol has been reported to be 28-109 times as potent as albuterol and safe at doses of 54ug in healthy subjects and asthmatics. Racemic formoterol structurally has 2 chiral centers and thus is composed of 4 enantiomers. The RR form (or arformoterol) is the active bronchodilator and it is not clear what the physiologic actions of the other 3 enantiomers are. This study is the first to evaluate nebulized arformoterol solution for therapy of acute asthmatics presenting to the Emergency Department.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital Emergency Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent
• FEV1 between 20 and 60% predicted after having received 5 mg of albuterol and 0.5 mg of atrovent as nebulized standard of care therapy
• Male or female between the ages of 18 and 45
• Asthma diagnosed by a physician and present for at least 6 months
• oxygen saturation greater or equal to 90% on room air
• Non smoker or < 10 pack-year history
• No other cause for wheezing/sob as determined by the treating physician

Exclusion Criteria:

• Clinical evidence or history of hepatic, renal, cardiovascular, GI, endocrine, metabolic or CNS disease which might interfere with the conduct of the study
• Acute respiratory failure or other significant pathology of the pulmonary system
• Female subjects who are pregnant or lactating
• Currently receiving therapy for a psychiatric disorder
• Subjects with a known sensitivity to formoterol (racemic or RR) or albuterol (racemic or lev)
• History of hospitalization for asthma within 2 months or treatment for acute asthma in an ED within 2 weeks of study entry
• Past or current use of disallowed medications
• Participation in an investigational study within 30 days

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arformoterol 3 doses	Drug: arformoterol (RR formoterol); Group 1 will receive nebulized arformoterol 15 ug every 20 minutes for 3 doses. Group 2 will receive nebulized arformoterol 15 ug first dose and then placebo every 20 minutes for 2 doses.; Other Names: Brovana
Experimental: Arformoterol 1 dose, placebo 2 doses	Drug: arformoterol (RR formoterol); Group 1 will receive nebulized arformoterol 15 ug every 20 minutes for 3 doses. Group 2 will receive nebulized arformoterol 15 ug first dose and then placebo every 20 minutes for 2 doses.; Other Names: Brovana; Drug: placebo; Group 2 will receive nebulized arformoterol 15 ug first dose and then placebo every 20 minutes for 2 doses.
Active Comparator: Levalbuterol 3 doses	Drug: levalbuterol; Group 3 will receive nebulized levalbuterol 1.25 mg every 20 minutes for 3 doses.; Other Names: Xopenex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Averaged Mean Percent Change From Baseline FEV1 and PEFR (Percent Predicted and Absolute) After the 3 Doses of Study Drug	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Mean Percent Change From Baseline in the FEV1 and PEFR (Absolute and Percent Predicted) Following Each Dose of Study Drug		1 hour
The Peak Change (Liters) and Peak Percent Change From Baseline in the FEV1 and PEFR (Absolute and Percent Predicted) Following Each Dose of Study Drug		1 hour
The Time to Onset of a 15% Improvement in FEV1 for Each Dose (Individual and Cumulative) and Total Dose of Study Medication to Reach This		5 hour
The Time Required to Achieve a FEV1 and PEFR > 60% Predicted for Each Dose (Individual and Cumulative)		5 hours
Percent of Responders (Defined as Those Discharged Following Treatment Who Did Not Require Additional Therapy in the ED)	The 2 subjects enrolled were both discharged home after study protocol completion, with no further treatment required in the ED setting.	5 hours
Percent of Patients in Each Group Requiring Additional Therapies After the First Hour of Study Drug Treatments	2 subjects were enrolled. Neither required additional asthma treatment after the 1st hour of study drug teatments.	5 hours
All of the Primary and Secondary Endpoints Partitioned by the Presenting PFT in Quartiles and the Presenting S Albuterol Levels in Quartiles		5 hours
Pharmacokinetics of Arformoterol in This Clinical Setting		5 hours
Most Effective Dose of Inhalation Arformoterol for Treating Acute Bronchospasm in Asthmatics by Evaluating the Averaged Mean Percent Change From Baseline % Predicted FEV1 After 3 Doses of Study Medication in Each of the 3 Groups	The study was terminated early and therefore secondary outcome measures were not obtained.	1 hour
Number of Participants Treated With Arformoteral in Acute Asthma Exacerbation as a Measure of Safety and Tolerability.	The study was terminated early and therefore secondary outcome measures were not obtained.	5 hours
The Mean Change From Baseline in the FEV1 and PEFR (Absolute and Percent Predicted) Following Each Dose of Study Drug	The study was terminated early and therefore secondary outcome measures were not obtained.	1 hour

Collaborators and Investigators

• Sponsor: Henry Ford Health System
• Collaborators: Sunovion
• Investigators: Principal Investigator: Richard M Nowak, MD, Henry Ford Health System

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 8, 2009
• First Submitted That Met QC Criteria: January 8, 2009
• First Posted (Estimate): January 9, 2009

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Acute asthma; Arformoterol; Long acting beta agonists
• 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; Formoterol Fumarate
• Other Study ID Numbers: ASRC947