Study to Assess Efficacy and Safety of Aclidinium Bromide and Aclidinium Bromide/Formoterol Fumarate in Stabile COPD Patients

COPD Clinical Trial

— AVANT  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03022097
• Other study ID #: D6570C00002
• Secondary ID: M-AS464-30
• Status: Completed
• Phase: Phase 3
• Start date: January 24, 2017
• Est. completion date: April 14, 2022

Study information

• Verified date: May 2022
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1067
• Est. completion date: April 14, 2022
• Est. primary completion date: April 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• COPD

Intervention

Drug:
• Aclidinium bromide/formoterol Fixed-Dose Combination
Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination, twice per day via Genuair
• Aclidinium bromide
Inhaled Aclidinium bromide 400 µg, twice per day via Genuair
• Formoterol Fumarate
Inhaled Formoterol Fumarate 12 µg, twice per day via Turbuhaler
• Placebo
Inhaled dose-matched placebo, twice per day via Genuair or via Turbuhaler

Locations

Country	Name	City	State
China	Research Site	Anhui
China	Research Site	Baotou
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Cangzhou
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Hefei
China	Research Site	Hengyang
China	Research Site	Hohhot
China	Research Site	Liangyugang
China	Research Site	Linhai
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Qiqihar
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanxi
China	Research Site	Shengyang
China	Research Site	Shenzhen
China	Research Site	Shenzhen
China	Research Site	Shijiazhuang
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Wenzhou
China	Research Site	Wuxi
China	Research Site	Xiamen
China	Research Site	Xian
China	Research Site	Xining
China	Research Site	Yangzhou
China	Research Site	Yanji
China	Research Site	Yinchuan
China	Research Site	Zhanjiang
India	Research Site	Ahmedabad
India	Research Site	Alappuzha
India	Research Site	Ernakulam
India	Research Site	Guntur
India	Research Site	Jaipur
India	Research Site	Kozhikode
India	Research Site	Mysore
India	Research Site	Nagpur
India	Research Site	Nagpur
India	Research Site	Nagpur
India	Research Site	Pune
India	Research Site	Pune
India	Research Site	Pune
India	Research Site	Vijayawada
Philippines	Research Site	Caloocan City
Philippines	Research Site	Iloilo City
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Taiwan	Research Site	Keelung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh City
Vietnam	Research Site	Ho Chi Minh City

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

China,  India,  Philippines,  Taiwan,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in 1-hour morning post-dose dose Forced expiratory volume in 1 second (FEV1)	Change from baseline in 1-hour morning post-dose dose FEV1 of Aclidinium bromide 400 µg/Formoterol fumarate 12 µg compared to Aclidinium bromide at Week 24.	Week 24
Primary	Change from baseline in morning pre-dose (trough) FEV1	Change from baseline in morning pre-dose (trough) FEV1 of Aclidinium bromide 400 µg/Formoterol fumarate 12 µg compared to Formoterol fumarate at Week 24.	Week 24
Primary	Change from baseline in trough FEV1	Change from baseline in trough FEV1 of Aclidinium bromide 400 µg compared to placebo at Week 24.	Week 24
Secondary	Change from baseline in peak FEV1	Change from baseline in peak FEV1 of Aclidinium bromide 400 µg compared to placebo at week 24	Week 24
Secondary	Improvements Transition Dyspnoea Index (TDI) focal score	Improvements TDI focal score of Aclidinium bromide 400 µg/Formoterol fumarate 12 µg and Aclidinium bromide 400µg compared to placebo at week 24	Week 24
Secondary	Change from baseline in St Georges Respiratory Questionnaire (SGRQ) total score	Change from baseline in SGRQ total score of Aclidinium bromide 400 µg/Formoterol fumarate 12 µg and Aclidinium bromide 400µg compared to placebo at week 24	Week 24