Clinical trial NCT03022097: Study to Assess Efficacy and Safety of Aclidinium Bromide and Aclidinium Bromide/Formoterol Fumarate in Stabile COPD Patients
Official title: A 24-week Treatment, Randomised, Parallel-group, Double Blinded, Double-Dummy, Multicenter Study to Assess the Efficacy and Safety of Aclidinium Bromide/Formoterol Fumarate Compared With Individual Components and Placebo and Aclidinium Bromide Compared With Placebo When Administered to Patients With Stable Chronic Obstructive Pulmonary Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COPD
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2017-01-16
Enrollment: 1625
Sex: ALL
Minimum age (years): 40
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multiple dose, randomised, parallel, double blind, double dummy, multicentre and multinational Phase III study to determine the efficacy and safety of Aclidinium bromide/Formoterol fumarate compared with individual components and placebo and Aclidinium bromide compared with Placebo when administered to patients with stable Chronic Obstructive Pulmonary Disease (COPD).


Eligibility criteria: Inclusion Criteria:

* 1. Adult male or non-pregnant, non-lactating female patients aged ≥40
* 2. Patients with a diagnosis of COPD prior to Visit 1 (screening)
* 3. Patients with moderate to severe stable COPD (Stage II or Stage III) at Visit 1: post-bronchodilator FEV1 ≥30% and \< 80% and post-bronchodilator FEV1/Forced vital capacity (FVC) \< 70%
* 4. Current or former smokers with a smoking history of ≥ 10 pack-years
* 5. Patients able to perform repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005 criteria at Visit 1(screening)
* 6. Patients who understand the study procedures and are willing to participate in the study as indicated by signing the informed consent

Exclusion Criteria:

* 1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff) or patients employed by or relatives of the employees of the site or sponsor.
* 2. Previous enrolment or randomisation in the present study
* 3. History or current diagnosis of asthma
* 4. Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening or during the run-in period
* 5. Patients hospitalized for COPD exacerbation (an emergency room visit for longer than 24 hours will be considered a hospitalization) within 3 months prior to screening and during the run-in period
* 6. Clinically significant respiratory conditions other than COPD
* 7. Patients who in the Investigator's opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to screening
* 8. Use of long-term oxygen therapy (≥15 hours/day)
* 9. Patient who does not maintain regular day/night, waking/sleeping cycles including night shift workers
* 10. Clinically significant cardiovascular conditions
* 11. Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated hypertension
* 12. Patients with QT corrected interval (QTc) using Fridericia formula (QTcF) (QTc=QT/ Duration in milliseconds between two R peaks of two consecutive QRS complexes (RR1/3) \>470 msec as indicated in the centralised reading report assessed at Screening (Visit 1)
* 13. Patients with clinically significant abnormalities in the clinical laboratory tests, ECG parameters (other than QTcF) or in the physical examination at Visit 1 (screening)
* 14. Patients with abnormal liver function tests defined as Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), or total bilirubin ≥ 2.5 times upper limit of normal ranges at screening
* 15. Patient with known non-controlled history of infection with human immunodeficiency virus and/or active hepatitis
* 16. Patient with a history of hypersensitivity reaction to inhaled anticholinergic drugs, sympathomimetic amines, inhaled medication or any component thereof
* 17. Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy
* 18. History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer
* 19. Any other serious or uncontrolled physical or mental dysfunction
* 20. Patients with a history (within 2 years prior to Visit 1 (screening) of drug and/or alcohol abuse that may prevent study compliance based on the Investigator judgment
* 21. Patients unlikely to be cooperative or cannot comply with the study procedures
* 22. Patients treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to screening
* 23. Patients who intended to use any concomitant medication not permitted by this protocol or who had not undergone the required washout period for a particular prohibited medication
* 24. Patients unable to give consent, or patients of consenting age but under guardianship, or vulnerable patients
* 25. Any other conditions that, in the Investigator's opinion, might have indicated the patient to be unsuitable for the study

Primary outcomes:
measure: Change From Baseline in 1-hour Morning Post Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Week 24, 1-hour morning post-dose
measure: Change From Baseline in Morning Pre-dose (Trough) FEV1 for Aclidinium Bromide/Formoterol Fumarate
timeFrame: Week 24, morning pre-dose (trough)
measure: Change From Baseline in Morning Pre-dose (Trough) FEV1 for Aclidinium Bromide
timeFrame: Week 24, morning pre-dose (trough)
Secondary outcomes:
measure: Change From Baseline in Peak FEV1
timeFrame: Week 24, peak
measure: Improvements Transition Dyspnoea Index (TDI) Focal Score
timeFrame: Week 24
measure: Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total Score
timeFrame: Week 24
Other outcomes:
Locations:
city: Baotou
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Cangzhou
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hengyang
country: China
facility: Research Site
city: Hohhot
country: China
facility: Research Site
city: Liangyugang
country: China
facility: Research Site
city: Linhai
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Qiqihar
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanxi
country: China
facility: Research Site
city: Shengyang
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Xian
country: China
facility: Research Site
city: Xining
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Yanji
country: China
facility: Research Site
city: Yinchuan
country: China
facility: Research Site
city: Zhanjiang
country: China
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Alappuzha
country: India
facility: Research Site
city: Ernakulam
country: India
facility: Research Site
city: Guntur
country: India
facility: Research Site
city: Jaipur
country: India
facility: Research Site
city: Kozhikode
country: India
facility: Research Site
city: Mysore
country: India
facility: Research Site
city: Nagpur
country: India
facility: Research Site
city: Nagpur
country: India
facility: Research Site
city: Nagpur
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Vijayawada
country: India
facility: Research Site
city: Caloocan City
country: Philippines
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Keelung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh City
country: Vietnam
facility: Research Site
city: Ho Chi Minh City
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
References: