Clinical Trials/NCT01437397

NCT01437397

Completed

Phase 3

A Phase III, Randomized, Double-blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Tolerability of Two Fixed Dose Combinations of Aclidinium Bromide/Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo for 24- Weeks Treatment in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease (COPD).

AstraZeneca222 sites in 1 country1,692 target enrollmentSeptember 2011

ConditionsChronic Obstructive Pulmonary Disease

InterventionsAclidinium Bromide/Formoterol Fumarate Aclidinium Bromide Formoterol Fumarate Placebo

DrugsAclidinium Bromide/Formoterol Fumarate Aclidinium Bromide Formoterol Fumarate Placebo

Overview

Phase: Phase 3
Intervention: Aclidinium Bromide/Formoterol Fumarate
Conditions: Chronic Obstructive Pulmonary Disease
Sponsor: AstraZeneca
Enrollment: 1692
Locations: 222
Primary Endpoint: Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1)
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this Phase III study is to assess the maintenance bronchodilator effects of the fixed dose combination versus monotherapies. This study will also assess the effects of the fixed dose combination in terms of COPD symptoms, disease related health status and the long-term safety and tolerability of the fixed dose combination. This study will include a 24 week treatment period, preceding by a run-in period, followed by a two week follow up visit. All patients will be randomized to one of four treatment arms or placebo.

Registry

clinicaltrials.gov

Start Date

September 2011

End Date

February 2013

Last Updated

9 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female patients at least 40 years of age
•Current or former cigarette smoker with a cigarette smoking history of at least 10 pack-years
•A diagnosis of stable moderate to severe COPD and stable airway obstruction as defined by the GOLD guidelines and stable airway obstruction. Patients had to have a postbronchodilator FEV1/FVC ratio \< 70% at Visit 1 (GOLD, 2010)
•Post-albuterol/salbutamol FEV1 values ≥ 30% and \< 80% of predicted value. FEV1 was measured at the Screening Visit (Visit 1) 10 to 15 minutes after inhalation of albuterol/salbutamol. Predicted normal used for calculation purposes were based on National Health and Nutrition Examination Survey III predicted values (Hankinson et al, 1999)
•Able to perform acceptable and repeatable pulmonary function testing for FEV1 according to ATS/ERS criteria (Miller et al, 2005) at Screening Visit (Visit 1) and throughout their participation in the trial
•Negative serum β-human chorionic gonadotropin pregnancy test at Visit 1 and must have been using hormonal contraceptives or a barrier method plus a spermicidal agent; otherwise at least 1-year postmenopausal or surgically sterile, defined as having a hysterectomy or tubal ligation (applied to female patients only)
•Judged by the Principal Investigator to be in otherwise good stable health based on medical history, physical examination, ECGs, and routine laboratory data evaluations
•Patients previously randomized in an aclidinium monotherapy trial were permitted as long as it had been at least 6 months since the completion of their previous trial participation
•Able to understand the study procedures and be willing to participate in the study as indicated by signing the informed consent

Exclusion Criteria

•Hospitalization for an acute COPD exacerbation within 3 months before Visit 1
•Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the 6 weeks before Visit
•Patients who developed a respiratory tract infection or COPD exacerbation during the washout or run-in period were discontinued from the study before randomization
•Any clinically significant respiratory conditions other than COPD, including active tuberculosis, history of interstitial lung disease, pulmonary thromboembolic disease, history of α1-antitrypsin deficiency, pulmonary resection, lung volume surgery, or any other thoracic surgery during the past 12 months, history of bronchiectasis secondary to respiratory diseases other than COPD (eg, cystic fibrosis, Kartagener syndrome), post organ transplantation, or expected to require thoracotomy or other lung surgery during the study
•Clinical history suggesting that the patient had asthma as opposed to COPD (Study Physician was to be contacted to discuss eligibility, if necessary)
•Chronic use of oxygen therapy ≥ 15 hours/day
•Body mass index(BMI) ≥ 40 kg/m2
•Patients who intended to start a pulmonary rehabilitation program during the trial were excluded, as well as those who finished or started it within 3 months prior to Screening Visit
•Clinically significant cardiovascular conditions including: myocardial infarction within the previous 6 months; newly diagnosed arrhythmia within the previous 3 months; unstable angina; unstable arrhythmia that had required changes in pharmacological therapy or other intervention within the previous 6 months; the presence of an automated implantable cardioverter-defibrillator; history of thoracic surgery within the past year before screening; hospitalization within the previous 12 months for heart failure of New York Heart Association functional class III (marked limitation of physical activity and only comfortable at rest, less than ordinary activity causes fatigue, palpitation or dyspnea), or class IV (unable to carry out any physical activity without discomfort) (Criteria Committee of the New York Heart Association criteria, 1994)
•Any uncontrolled infection that may have placed the patient at risk resulting from human immunodeficiency virus, active hepatitis and/or patients with diagnosed active tuberculosis

Arms & Interventions

1

Aclidinium/formoterol Fixed Dose Combination (FDC) 400/12μg

Intervention: Aclidinium Bromide/Formoterol Fumarate

2

Aclidinium/formoterol Fixed Dose Combination (FDC) 400/6μg

Intervention: Aclidinium Bromide/Formoterol Fumarate

3

Aclidinium monotherapy 400 μg

Intervention: Aclidinium Bromide

4

Formoterol monotherapy 12 μg

Intervention: Formoterol Fumarate

5

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1)

Time Frame: Week 24 of treatment

Change From Baseline in Morning Trough Forced Expiratory Volume in One Second (FEV1)

Time Frame: Week 24 of treatment

Secondary Outcomes

Change in Transition Dyspnea Index (TDI) Focal Score(Week 24 of treatment)
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score(Week 24 of treatment)