Efficacy and Safety Study of Two Fixed-dose Combinations of Aclidinium Bromide With Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo (LAC-MD-27)

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)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Aclidinium 400 μg / Formoterol 12 μg; Drug: Aclidinium 400 μg / Formoterol 6 μg; Drug: Aclidinium 400 μg; Drug: Formoterol 12 μg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Forest Investigative Site 0909
    • Pheonix, Arizona, United States, 85006
      • Forest Investigative Site 2050
  • California
    • Rancho Mirage, California, United States, 92270
      • Forest Investigative Site 2029
    • Stockton, California, United States, 95207
      • Forest Investigative Site 1084
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Forest Investigative Site 2045
  • Florida
    • Clearwater, Florida, United States, 33765
      • Forest Investigative Site 1152
    • Tampa, Florida, United States, 33603
      • Forest Investigative Site 2053
    • Tampa, Florida, United States, 33613
      • Forest Investigative Site 2047
  • Massachusetts
    • N. Dartmouth, Massachusetts, United States, 02747
      • Forest Investigative Site 1431
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Forest Investigative Site 2084
  • New York
    • Elmira, New York, United States, 14901
      • Forest Investigative Site 1119
  • North Carolina
    • Elizabeth city, North Carolina, United States, 27909
      • Forest Investigative Site 2035
    • Raleigh, North Carolina, United States, 27607
      • Forest Investigative Site 1153
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Forest Investigative Site 2028
  • Oregon
    • Medford, Oregon, United States, 97504
      • Forest Investigative Site 2043
    • Portland, Oregon, United States, 97213
      • Forest Investigative Site 1106
  • Rhode Island
    • E. Providence, Rhode Island, United States, 02914
      • Forest Investigative Site 1089
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Forest Investigative Site 1121
  • Texas
    • San Antonio, Texas, United States, 78215
      • Forest Investigative Site 1498
    • Waco, Texas, United States, 76712
      • Forest Investigative Site 1129

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 β-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), β2 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 Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aclidinium 400 μg / Formoterol 12 μg; Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID)	Drug: Aclidinium 400 μg / Formoterol 12 μg; Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID) for a 14 day period within four different treatment periods.
Experimental: Aclidinium 400 μg / formoterol 6 μg; Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID)	Drug: Aclidinium 400 μg / Formoterol 6 μg; Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID) for a 14 day period within four different treatment periods.
Experimental: Aclidinium 400 μg; Aclidinium bromide 400 μg administered twice-daily (BID)	Drug: Aclidinium 400 μg; Aclidinium bromide 400 μg administered twice-daily (BID) for a 14 day period within four different treatment periods.
Active Comparator: Formoterol 12 μg; Formoterol fumarate 12 μg twice-daily	Drug: Formoterol 12 μg; Formoterol fumarate 12 μg twice-daily for a 14 day period within four different treatment periods.
Placebo Comparator: Placebo; Placebo twice-daily	Drug: Placebo; Placebo twice-daily delivered by inhalation for a 14 day period within four different treatment periods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12)	0 to 12 hours post-dose on Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1)	Day 14
Change From Baseline in Morning Peak Forced Expiratory Volume in One Second (FEV1)	Day 14

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• lac-md-27-synopsis

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: January 13, 2010
• First Submitted That Met QC Criteria: January 13, 2010
• First Posted (Estimate): January 14, 2010

Study Record Updates

• Last Update Posted (Actual): February 28, 2017
• Last Update Submitted That Met QC Criteria: January 16, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; Chronic Bronchitis; Emphysema; Airflow Obstruction, Chronic; Chronic Airflow Obstruction; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease
• 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; Formoterol Fumarate
• Other Study ID Numbers: LAC-MD-27