Efficacy and Safety Study of Two Fixed-dose Combinations of Aclidinium Bromide With Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo

Chronic Obstructive Pulmonary Disease Clinical Trial

— LAC-MD-27  

Official title:

Efficacy and Safety Study of Two Fixed-Dose Combinations of Aclidinium Bromide With Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate, and Placebo All Administered Twice Daily (BID) to Patients With Stable, Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01049360
• Other study ID #: LAC-MD-27
• Status: Completed
• Phase: Phase 2
• First received: January 13, 2010
• Last updated: September 30, 2011
• Start date: December 2009
• Est. completion date: September 2010

Study information

• Verified date: September 2011
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of this multicenter, randomized, double-blind, placebo-controlled, 4-period, incomplete-block crossover, dose-ranging study comparing 2 fixed dose combinations (FDCs) of aclidinium bromide with formoterol fumarate or with placebo, aclidinium bromide and formoterol fumarate, all administered twice a day (BID) in patients with stable, moderate to severe chronic obstructive pulmonary disease (COPD) beginning with a 2-week run-in period and with a 7-10 day washout each between treatment period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: September 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Understand the study procedures and be willing to participate in the study as indicated by signing the ICF and HIPAA form

• Be male or female aged 40 to 80 years, inclusive

• Have a diagnosis of stable, moderate to severe COPD (stages II and III) as defined by guidelines of the Global Initiative for Chronic Obstructive Lung Disease (2008)

• Be a current or former cigarette smoker with a smoking history of at least 10 pack-years

• Have post-albuterol/salbutamol FEV1 values = 30% and < 80% of the predicted value. FEV1 will be measured at the Screening Visit (Visit 1) between 10 and 15 minutes after inhalation of albuterol/salbutamol.

• Have post-albuterol/salbutamol FEV1/FVC values < 70% (ie, 100 × post- albuterol/salbutamol FEV1/FVC < 70%).

• If female, be at least 1 year postmenopausal or surgically sterile (defined as having a hysterectomy or tubal ligation). Women of childbearing potential must have a negative serum ß-human chorionic gonadotropin pregnancy test at screening

• Be in good stable health (as judged by the Investigator) other than the COPD, based on medical history, physical examination, ECG, spirometry, and clinical laboratory data evaluations

• Have COPD symptoms and FEV1 values at the time of randomization that are stable compared with those at Screening (Visit 1), according to the Investigator's medical judgment

Exclusion Criteria:

• Have been hospitalized for an acute COPD exacerbation within 3 months before screening

• Have any respiratory tract infection (including the upper respiratory tract) or signs of a COPD exacerbation or respiratory infection in the 6 weeks before Screening (Visit 1).

• Have any clinically significant respiratory conditions other than COPD

• Have a history or presence of asthma verified from medical records

• Have used theophylline (including long-acting theophylline) within the previous 3 months before study entry

• Have Stage II hypertension, defined as systolic pressure of 160 and above, and diastolic pressure of 100 and above

• Chronic use of oxygen therapy = 15 hours a day

• Have a history, current diagnosis, or presence of exercise-induced bronchospasm

• Have a body mass index = 40 kg/m2

• Have participated in an pulmonary rehabilitation program within the previous 3 months

• Have clinically significant cardiovascular conditions

• Have uncontrolled infection resulting from human immunodeficiency virus and/or active hepatitis

• Have symptomatic prostatic hypertrophy and/or bladder neck obstruction.

• Have narrow-angle glaucoma

• Have a history of hypersensitivity reaction (including report of paradoxical bronchospasm) to inhaled anticholinergics (including aclidinium bromide), ß2 adrenergic agonists, or any other inhaled medication or any component thereof

• Have a QTcB, as indicated in the centralized reading report, above 470 msec in the resting ECGs performed at Screening (Visit 1) and/or patients who are using medications that may prolong the QT interval

• Have clinically relevant abnormalities in the results of clinical laboratory tests, in ECG parameters other than QTc, in results of the physical examination,

• Have any concurrent medical condition that, in the judgment of the Investigator, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being

• Do not maintain regular day/night, waking/sleeping cycles (eg, patients with history of sleep apnea syndrome or any disease related with sleep disturbances such as restless legs syndrome or somnambulism)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• aclidinium bromide/formoterol fumarate combination
Aclidinium bromide with 2 dose levels of Formoterol fumarate compared with placebo, aclidinium bromide and formoterol fumarate delivered by inhalation twice daily for a 14 day period within four different treatment periods.
• aclidinium bromide/formoterol fumarate combination
Aclidinium bromide with 2 dose levels of Formoterol fumarate compared with placebo, aclidinium bromide and formoterol fumarate delivered by inhalation wice daily for a 14 day period within four different treatment periods.
• aclidinium bromide
Aclidinium bromide with 2 dose levels of Formoterol fumarate compared with placebo, aclidinium bromide and formoterol fumarate delivered by inhalation twice daily for a 14 day period within four different treatment periods.
• formoterol fumarate
Aclidinium bromide with 2 dose levels of Formoterol fumarate compared with placebo, aclidinium bromide and formoterol fumarate delivered twice daily for a 14 day period within four different treatment periods.
• placebo
Aclidinium bromide with 2 dose levels of Formoterol fumarate compared with placebo, aclidinium bromide and formoterol fumarate delivered by inhalation twice daily for a 14 day period within four different treatment periods.

Locations

Country	Name	City	State
United States	Forest Investigative Site 2028	Cincinnati	Ohio
United States	Forest Investigative Site 1152	Clearwater	Florida
United States	Forest Investigative Site 1089	E. Providence	Rhode Island
United States	Forest Investigative Site 2035	Elizabeth city	North Carolina
United States	Forest Investigative Site 1119	Elmira	New York
United States	Forest Investigative Site 0909	Glendale	Arizona
United States	Forest Investigative Site 2043	Medford	Oregon
United States	Forest Investigative Site 1431	N. Dartmouth	Massachusetts
United States	Forest Investigative Site 2050	Pheonix	Arizona
United States	Forest Investigative Site 1106	Portland	Oregon
United States	Forest Investigative Site 1153	Raleigh	North Carolina
United States	Forest Investigative Site 2029	Rancho Mirage	California
United States	Forest Investigative Site 1498	San Antonio	Texas
United States	Forest Investigative Site 1121	Spartanburg	South Carolina
United States	Forest Investigative Site 1084	Stockton	California
United States	Forest Investigative Site 2084	Summit	New Jersey
United States	Forest Investigative Site 2047	Tampa	Florida
United States	Forest Investigative Site 2053	Tampa	Florida
United States	Forest Investigative Site 1129	Waco	Texas
United States	Forest Investigative Site 2045	Wheat Ridge	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
Forest Laboratories	Almirall, S.A.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary efficacy assessment will be the change from baseline in normalized forced expiratory volume in 1 second (FEV1).		14 day time frame per treatment period	No
Primary	AUC0-12 measured over the 12 hours after morning dose of Investigational Product(IP) at Day 14 on treatment.		14 day time frame per treatment period	No
Secondary	The secondary efficacy assessments will be the change from baseline in morning predose FEV1 and the change from baseline in morning peak FEV1, both at Day 14 on treatment.		14 day time frame per treatment period	No