A Dose Ranging Study of Arformoterol Given Once Daily Compared to Arformoterol Given Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD) - Full Text View

Sponsor:	Sepracor, Inc.
Information provided by:	Sepracor, Inc.
ClinicalTrials.gov Identifier:	NCT00691405

Purpose

A dose ranging study to evaluate the safety, tolerability and efficacy of arformoterol (given once or twice a day) in subjects with COPD.

Condition	Intervention	Phase
COPD	Drug: Arformoterol tartrate inhalation solution Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Efficacy Study
Official Title:	A Double-Blind, Randomized, Multicenter, Two-Part Parallel-Group, Dose-Ranging Study of Twice-Daily and Once-Daily (R,R) Formoterol in the Treatment of Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Formoterol fumarate Arformoterol Formoterol Arformoterol Tartrate

U.S. FDA Resources

Further study details as provided by Sepracor, Inc.:

Primary Outcome Measures:

Part A: The primary efficacy endpoint is the time-normalized area under the FEV1 percent change from pre-dose curve over 12 hours (nAUC0-12) after the first (AM) dose at the 24 hour clinic visit (Visit 4) following 14 days of double-blind treatment. [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
Part B: The primary efficacy endpoint is the time-normalized area under the FEV1 percent change from pre-dose curve over 24 hours (nAUC0-24) at the 24 hour clinic visit (Visit 7) following 14 days of double-blind treatment. [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Relationship between plasma concentrations of arformoterol and changes in ECG QTc intervals at steady state throughout the dosing interval. [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: Yes ]
Part A only: Time-normalized area under the curve for FEV1 percent change from pre-dose over 24 hours (nAUC0-24) for each 24 hour clinic visit. [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), ] [ Designated as safety issue: No ]
Part B only: Time-normalized area under curve for the FEV1 percent change from pre-dose over 12 hours (nAUC0-12) for each 24 hour clinic visit. [ Time Frame: Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
Time-normalized area under the curve for the percent change in FEV1 from pre-dose over 6 hours (nAUC0-6) for the 6 hour clinic visit (Visits 3 and 6). [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
Percent change in FEV1 from pre-dose to each post dose time point [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
Peak percent change in FEV1 post-dose [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
Ipratropium bromide metered-dose inhaler (MDI) use and racemic albuterol MDI use [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
Morning and evening peak expiratory flow rate (PEFR) [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
Exacerbations of COPD [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: Yes ]
COPD symptom ratings [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
Effects of withdrawal from therapy [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: Yes ]
Relationship between plasma concentrations of (R,R)-formoterol and selected pharmacodynamic parameters. [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]
FEV1 percent change from pre-dose (24-hour trough) following 14 days of double-blind treatment. [ Time Frame: Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 21), Visit 6 (Day 28), Visit 7 (Day 42), Visit 8 (Day 48) ] [ Designated as safety issue: No ]

Enrollment:	215
Study Start Date:	October 2003
Study Completion Date:	May 2004
Primary Completion Date:	May 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A1: Experimental Arformoterol 5 mcg BID for 14 days	Drug: Arformoterol tartrate inhalation solution Arformoterol 5 mcg BID
A2: Experimental Arformoterol 15 mcg BID for 14 days	Drug: Arformoterol tartrate inhalation solution Arformoterol 15 mcg BID
A3: Experimental Arformoterol 25 mcg BID for 14 days	Drug: Arformoterol tartrate inhalation solution Arformoterol 25 mcg BID
A4: Placebo Comparator Placebo inhalation solution BID for 14 days	Drug: Placebo Placebo inhalation solution BID
B1: Experimental Arformoterol 15 mcg QD for 14 days	Drug: Arformoterol tartrate inhalation solution Arformoterol 15 mcg QD
B2: Experimental Arformoterol 25 mcg QD for 14 days	Drug: Arformoterol tartrate inhalation solution Arformoterol 25 mcg QD
B3: Experimental Arformoterol 50 mcg QD for 14 days	Drug: Arformoterol tartrate inhalation solution Arformoterol 50 mcg QD
B4: Placebo Comparator Placebo inhalation solution QD for 14 days	Drug: Placebo Placebo inhalation solution QD

Detailed Description:

This study is a double-blind, repeat-dose, randomized, multicenter, two-part, parallel-group, dose-ranging study of arformoterol and placebo in the treatment of subjects with COPD. Approximately 215 subjects will be randomized in this study. Study participation will consist of a total of eight (8) study visits over approximately ten (10) weeks for each subject.

Eligibility

Ages Eligible for Study:	35 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject may be male or female and must be aged greater than or equal to 35 years on the day the informed consent is signed.
Female subject less than or equal to 65 years of age must have a serum pregnancy test conducted at study start and confirmed negative. Subjects of childbearing potential must be using an acceptable method of birth control and agree to continue its use throughout the study.
In order to be considered not of childbearing potential female subjects must be:
- documented surgically sterile (defined as status post-hysterectomy or bilateral tubal ligation) OR
- postmenopausal
Subject must have a primary diagnosis of COPD, which may include components of chronic bronchitis and/or emphysema. Diagnosis can be made during the screening process.
Subject must have a minimum smoking history of 15 pack-years (pack-years = the number of cigarette packs per day times the number of years).
Subject must have a chest x-ray that is consistent with the diagnosis of COPD (e.g., not diagnostic of pneumonia, other infection, atelectasis, or pneumothorax) and taken less than or equal to 6 months before study start. If there is no chest x-ray taken less than or equal to 6 months before study start, a chest x-ray will be performed at Visit 1.
Subject must be able to complete all study questionnaires and logs reliably.

Exclusion Criteria:

A female who is pregnant or lactating.
Subject who has participated in an investigational drug study within 30 days prior to study start, or who is currently participating in another investigational drug study.
Subject's schedule or travel prevents the completion of all required visits.
Subject is scheduled for in-patient hospitalization, including elective surgery (in patient or out-patient) during the trial.
Subject has had a life-threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the 30 days prior to study start.
Subject has a known history of asthma (except childhood asthma) or any chronic respiratory disease (including a current history of sleep apnea) other than COPD (chronic bronchitis and/or emphysema).
Subject has a known history of alpha 1 antitrypsin deficiency-related emphysema.
Subject has a history of cancer except non-melanoma skin cancer. Subjects with a history of cancer that is considered surgically cured and without a recurrence within the past 5 years may participate in the study. History of hematologic/lymphatic malignancy treated with chemotherapy or radiation is not allowed, under any condition.
Subject has a history of lung resection of more than one full lobe or being a recipient of a lung or major organ transplant.
Subject requires continuous supplemental oxygen therapy (unless subject resides at elevation greater than or equal to 4,000 feet).
Subject has had a change in dose or type of any medications for COPD within 14 days before the screening visit.
Subject has a known sensitivity to arformoterol, ipratropium or albuterol or any of the excipients contained in any of these formulations.
Subject has a history of substance abuse within 12 months of Visit 1, or with a positive urine drug screen at study start.
Subject is using any prescription drug for which concomitant beta-agonist administration is contraindicated (e.g., beta-blockers).
Subject has had significant blood loss (>500 cc) or donated blood within 60 days preceding screening or plans to donate blood during or within 60 days after completing the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00691405

Show 31 Study Locations

Sponsors and Collaborators

Sepracor, Inc.

More Information

No publications provided

Responsible Party:	Sepracor Inc. ( Brovana Medical Director )
Study ID Numbers:	091-026
Study First Received:	June 2, 2008
Last Updated:	June 4, 2008
ClinicalTrials.gov Identifier:	NCT00691405 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Sepracor, Inc.:

Arformoterol
(R,R)-formoterol

Additional relevant MeSH terms:

Respiratory System Agents
Neurotransmitter Agents
Adrenergic beta-Agonists
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Asthmatic Agents
Adrenergic Agonists
Pharmacologic Actions

Lung Diseases, Obstructive
Respiratory Tract Diseases
Autonomic Agents
Therapeutic Uses
Lung Diseases
Formoterol
Peripheral Nervous System Agents
Bronchodilator Agents
Pulmonary Disease, Chronic Obstructive

ClinicalTrials.gov processed this record on November 27, 2009