Efficacy Safety Study of Arformoterol QD Dosing Versus BID Dosing in COPD

Modified-blind, Randomized, Multicenter, Single Dose, Two-way Crossover Study of Arformoterol Tartrate Inhalation Solution 15 Micrograms Twice A Day Versus 30 Micrograms Once A Day in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

To evaluate the efficacy and safety of arformoterol tartrate inhalation solution 30μg/4mL QD (two 15μg/2mL dosed in combination) over a 24-hour period compared to arformoterol tartrate inhalation solution 15μg/2 mL BID in subjects with COPD.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Arformoterol Tartrate Inhalation Solution; Drug: Arformoterol Tartrate Inhalation Solution; Drug: Placebo

Detailed Description

This is a modified blind, randomized, multicenter, single dose two-way crossover study to assess the efficacy and safety of arformoterol 15μg BID versus arformoterol 30μg QD in subjects with COPD. Subject participation will last approximately three weeks and will include a screening visit, two 24-hour visits, and a follow up telephone call. 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): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Medford, Oregon, United States, 97504
    • Portland, Oregon, United States, 97213
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects must be at least 45 years old at the time of consent.
• Subjects must have a pre-established primary clinical diagnosis of COPD.
• Subjects must have a baseline FEV1 of ≤ 65% of predicted normal value at Visit 1.
• Subjects must have a FEV1 ≥ 0.70L at Visit 1.
• Subjects must have a FEV1/forced vital capacity (FVC) ratio of ≤ 70% at Visit 1.

Exclusion Criteria:

• Subjects who do not have a 15 pack-year smoking history and a baseline breathlessness severity grade of 2 (as measured by the Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Screening.
• Subjects with life-threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days prior to Visit

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 15 mcg BID / 30 mcg QD; Arformoterol 15 microgram twice a day (BID) taken each morning and evening for one visit followed by Arformoterol 30 microgram once a day (QD) in the morning and placebo in the evening for the next visit.	Drug: Arformoterol Tartrate Inhalation Solution; Nebulized arformoterol tartrate inhalation solution 15 microgram twice a day (BID); Other Names: Brovana; Drug: Arformoterol Tartrate Inhalation Solution; Nebulized arformoterol tartrate inhalation solution 30 microgram once a day (QD); Other Names: Brovana; Drug: Placebo; Placebo inhalation solution (citrate buffered 0.9% saline solution) once a day
Experimental: 30 mcg QD / 15 mcg BID; Arformoterol 30 microgram once a day (QD) in the morning and placebo in the evening for one visit followed by Arformoterol 15 microgram twice a day (BID) in the morning and evening for the next visit.	Drug: Arformoterol Tartrate Inhalation Solution; Nebulized arformoterol tartrate inhalation solution 15 microgram twice a day (BID); Other Names: Brovana; Drug: Arformoterol Tartrate Inhalation Solution; Nebulized arformoterol tartrate inhalation solution 30 microgram once a day (QD); Other Names: Brovana; Drug: Placebo; Placebo inhalation solution (citrate buffered 0.9% saline solution) once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 24 Hours	Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken within 24 hours of dosing.	0-24 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 12 Hours	Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken within 12 hours of dosing.	0-12 hours
Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Between 12-24 Hours	Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken between 12 and 24 hours of dosing.	12-24 hours
Change in Forced Expiratory Volume in One Second From Pre-dose to the 24 Hour Time Point	Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change in FEV1 from pre-dose to the readings taken 24 hours post-dose, which represents the trough in dose level.	pre-dose and 24 hours post-dose
Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose	Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome offers the FEV1 readings taken pre-dose and at various time points within 24 hours post-dose.	pre-dose, immediately post-dose, 30 min, 1,2,4,6,8,10,12, 12.5,13,14,16,23,24 hours post first dose
Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose	Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome offers the change in FEV1 readings between pre-dose and various time points within 24 hours post-dose.	Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose
Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose	Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the percent of the estimated healthy lung function at specified time points.	Pre-dose, Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose
Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose	Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the change in percent of the estimated healthy lung function at specified time points compared to the pre-dose value.	Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose
Peak Percent of Predicted Forced Expiratory Volume at One Second (FEV1) Over 12 Hours Post-Dose.	Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the percent of the estimated healthy lung function and reports the highest percent found within 12 hours of dosing.	12 hours
Peak Change in Forced Expiratory Volume at One Second (FEV1) Within 12 Hours Post Dose Compared to Pre-dose	Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change in FEV1 from pre-dose to the readings taken 12 hours post-dose, and reports the largest change during that time.	12 hours
Time to Onset of 15 Percent Response Within 12 Hours of Dosing	Time to a 15 percent improvement in forced expiratory volume in one second (FEV1) within 12 hours of dosing. Only patients who achieved at least a 15 percent improvement are included.	12 hours post first dose
Time to Onset of Response of Both a 12 Percent Increase and 200 Milliliter Increase Within 12 Hours of Dosing	Time to a 12 percent improvement in forced expiratory volume in one second (FEV1) AND a 200 milliliter increase in FEV1 within 12 hours of dosing. Only patients who met both conditions are included	up to 12 hours post dose
Time to Onset of Response of Both a 12 Percent Increase and 200 Milliliter Increase in Forced Expiratory Volume in One Second Within 12 Hours of Dosing	Forced vital capacity is the total amount of air that can forcibly be blown out after full inspiration.	pre-dose, immediately post first dose, 30 min, 1,2,4,6,8,10,12, 12.5, 13, 14, 16, 23,24 hours post first dose
Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point	Forced vital capacity is the total amount of air that can forcibly be blown out after full inspiration. The measure compares the change from pre-dose reading to each post-dose time point.	immediately post first dose, 30 min, 1,2,4,6,8,10,12, 12.5, 13, 14, 16, 23,24 hours post first dose

Collaborators and Investigators

• Sponsor: Sunovion
• Investigators: Study Director: Pulmonary Medical Director, Sunovion

Publications and helpful links

General Publications

• Panettieri RA Jr, MacIntyre N, Sims M, Kerwin E, Fogarty C, Noonan M, Claus R, Andrews WT. Comparison of the efficacy and safety of arformoterol 15 microg twice daily and arformoterol 30 microg once daily in COPD: a single-dose, multicenter, randomized, modified-blind, two-way crossover study. Clin Ther. 2009 Aug;31(8):1716-23. doi: 10.1016/j.clinthera.2009.08.012.

Helpful Links

• Brovana Approved Labeling Text

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: December 10, 2007
• First Submitted That Met QC Criteria: December 10, 2007
• First Posted (Estimate): December 12, 2007

Study Record Updates

• Last Update Posted (Estimate): February 22, 2012
• Last Update Submitted That Met QC Criteria: February 21, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: COPD; Chronic Bronchitis; Emphysema
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; 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; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Pharmaceutical Solutions; Formoterol Fumarate
• Other Study ID Numbers: 091-903