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

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.

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).

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Aclidinium bromide/formoterol Fixed-Dose Combination; Drug: Aclidinium bromide; Drug: Formoterol Fumarate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1067
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui, China, 230061
    • Research Site
  • Baotou, China, 14010
    • Research Site
  • Beijing, China
    • Research Site
  • Beijing, China, 100050
    • Research Site
  • Beijing, China, 100097
    • Research Site
  • Beijing, China, CN-100083
    • Research Site
  • Cangzhou, China, 61000
    • Research Site
  • Changchun, China, 130021
    • Research Site
  • Changsha, China, 430033
    • Research Site
  • Changsha, China, 410005
    • Research Site
  • Chengdu, China, 610072
    • Research Site
  • Guangzhou, China, 510530
    • Research Site
  • Haikou, China, 570311
    • Research Site
  • Hangzhou, China, 310005
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Hangzhou, China, 310014
    • Research Site
  • Hefei, China, 230001
    • Research Site
  • Hefei, China, 230022
    • Research Site
  • Hengyang, China, 50012
    • Research Site
  • Hohhot, China, 010017
    • Research Site
  • Liangyugang, China, 222002
    • Research Site
  • Linhai, China, 317000
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Nanjing, China, 210009
    • Research Site
  • Qiqihar, China, 161005
    • Research Site
  • Shanghai, China, 200433
    • Research Site
  • Shanghai, China, 200030
    • Research Site
  • Shanghai, China, 200062
    • Research Site
  • Shanghai, China, 200090
    • Research Site
  • Shanghai, China, 200040
    • Research Site
  • Shanghai, China, 200240
    • Research Site
  • Shanghai, China, 201200
    • Research Site
  • Shanxi, China, 30001
    • Research Site
  • Shengyang, China, 110004
    • Research Site
  • Shenzhen, China, 518053
    • Research Site
  • Shenzhen, China, 518020
    • Research Site
  • Shijiazhuang, China, 050000
    • Research Site
  • Taiyuan, China, 030001
    • Research Site
  • Tianjin, China, 300052
    • Research Site
  • Wenzhou, China, 325015
    • Research Site
  • Wuxi, China, 214023
    • Research Site
  • Xiamen, China, 361004
    • Research Site
  • Xian, China, 710061
    • Research Site
  • Xining, China, 810007
    • Research Site
  • Yangzhou, China, 225000
    • Research Site
  • Yanji, China, 133000
    • Research Site
  • Yinchuan, China, 750004
    • Research Site
  • Zhanjiang, China, 524001
    • Research Site
• India
  • Ahmedabad, India, 380060
    • Research Site
  • Alappuzha, India, 688524
    • Research Site
  • Ernakulam, India, 683577
    • Research Site
  • Guntur, India, 522001
    • Research Site
  • Jaipur, India, 302006
    • Research Site
  • Kozhikode, India, 673008
    • Research Site
  • Mysore, India, 57002
    • Research Site
  • Nagpur, India, 440012
    • Research Site
  • Nagpur, India, 440010
    • Research Site
  • Nagpur, India, 440019
    • Research Site
  • Pune, India, 411019
    • Research Site
  • Pune, India, 411057
    • Research Site
  • Pune, India, 440012
    • Research Site
  • Vijayawada, India, 520 008
    • Research Site
• Philippines
  • Caloocan City, Philippines, 1400
    • Research Site
  • Iloilo City, Philippines, 5000
    • Research Site
  • Manila, Philippines, 1000
    • Research Site
  • Quezon City, Philippines, 1101
    • Research Site
  • Quezon City, Philippines, 1100
    • Research Site
  • Quezon City, Philippines, 1000
    • Research Site
• Taiwan
  • Keelung, Taiwan, 20448
    • Research Site
  • Taichung, Taiwan, 40201
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
• Vietnam
  • Hanoi, Vietnam, 10000
    • Research Site
  • Ho Chi Minh, Vietnam, 70000
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site
  • Ho Chi Minh City, Vietnam, 70000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 130 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Inhaled dose-matched placebo, twice per day via Genuair or via Turbuhaler
EXPERIMENTAL: Experimental 1; Aclidinium bromide 400μg/Formoterol fumarate 12 μg	Drug: Aclidinium bromide/formoterol Fixed-Dose Combination; Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination, twice per day via Genuair
EXPERIMENTAL: Experimental 2; Aclidinium bromide 400 μg	Drug: Aclidinium bromide; Inhaled Aclidinium bromide 400 μg, twice per day via Genuair
ACTIVE_COMPARATOR: Comparator; Formoterol fumarate 12 μg	Drug: Formoterol Fumarate; Inhaled Formoterol Fumarate 12 μg, twice per day via Turbuhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 24, 2017
• Primary Completion (ACTUAL): April 14, 2022
• Study Completion (ACTUAL): April 14, 2022

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: January 13, 2017
• First Posted (ESTIMATE): January 16, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Bromides; Formoterol Fumarate
• Other Study ID Numbers: D6570C00002; M-AS464-30 (OTHER: Astrazenca)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No