Evaluate the Effect of Aclidinium Bromide on Long-term Cardiovascular Safety and Exacerbations in Moderate to Very Severe COPD Patients. - ASCENT COPD

Study identifier:D6560C00002

ClinicalTrials.gov identifier:NCT01966107

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Double-blind, Randomized, Placebo-controlled, Parallel-group, Phase IV Study to Evaluate the Effect of Aclidinium Bromide on Long-term Cardiovascular Safety and COPD Exacerbations in Patients with Moderate to Very Severe COPD (ASCENT COPD)

Medical condition

COPD

Phase

Phase 4

Healthy volunteers

Study drug

Aclidinium Bromide, Placebo

Sex

All

Actual Enrollment

3635

Study type

Interventional

Age

40 Years - 130 Years

Date

Study Start Date: 16 Oct 2013

Primary Completion Date: 21 Sept 2017

Study Completion Date: 21 Sept 2017

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2018 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- 1. Male or female outpatients ≥ 40 years of age
- 2. Current or former cigarette smokers with a smoking history of at least 10 pack-years
- 3. A diagnosis of stable, moderate to very severe COPD (GOLD, 2015) with a post-bronchodilator FEV < 80% FEV1/forced vital capacity (FVC) ratio < 70%
- 4. Must have at least one of the following 4 criteria:
a. Documented cerebrovascular disease (stroke or transient ischemic attack, carotid stenosis)
b. Documented coronary artery disease (angina, MI, angioplasty/stent/bypass)
c. Documented peripheral vascular disease or history of claudication
d. At least 2 of the following atherothrombotic risk factors as determined by the PI:
1. Male ≥ 65 years or female ≥ 70 years
2. Diabetes
3. Dyslipidemia
4. Hypertension
5. Waist circumference inches males ≥ 40 in or in females ≥ 38 inches
6. Evidence of renal dysfunction (eGFR < 60) and microalbuminuria (eGFR is based on modification of diet in renal disease [MDRD] equation, microalbuminuria is defined as ≥ 30-300 mcg/mg creatinine on a spot urine or ≥30 mg creatinine on a 24hr urine test)
- 5. Maintained stable respiratory medications for 2 weeks prior to randomization (Appendix II)
- 6. Able to perform pulmonary function test (PFT) maneuvers and follow study procedures
- 7. Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (HCG) pregnancy test at Visit 1A and be practicing medically acceptable method of contraception. Otherwise, female patients should be at least 1 year postmenopausal, surgically sterile (defined as having a hysterectomy or tubal ligation).
- 8. Should understand study procedures and be willing to participate in the study as indicated by signing the ICF

Exclusion Criteria

- 1. Significant diseases other than COPD or cardiovascular disease (e.g., metastatic cancer) which, in the opinion of the PI, may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study
- 2. Unstable or life threatening cardiovascular disease or COPD as determined by the PI
- 3. Patients with comorbid lung disease such as asthma, cystic fibrosis, bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease
- 4. Planned lung transplant or lung volume reduction surgery
- 5. Currently treated with a combination of LAMA and LABA/ICS therapy.
- 6. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within 5 years prior to screening. Patients with treated basal cell and squamous cell (skin) carcinoma are allowed
- 7. Respiratory infection or COPD exacerbation at Screening and/or within 4 weeks prior to screening
- 8. Uncontrolled infection resulting from human immunodeficiency virus (HIV) and/or active hepatitis
- 9. Reported history of drug or alcohol abuse within the past 12 months
- 10. History of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical
bronchospasm)
- 11. History of acute urinary retention, treatment refractory benign prostatic hyperplasia (BPH), bladder neck obstruction, or narrow-angle glaucoma (Note: Patients with controlled, stable BPH are not excluded)
- 12. Patients unable to use a multidose DPI or a pressurized metered-dose inhaler
- 13. Treatment with any other investigational drug within 30 days (or 6 half-lives, whichever is longer) before Visit 1A
- 14. Women who are pregnant or breastfeeding
- 15. Use of any prohibited medication listed in Appendix II
- 16. Employee or immediate relative of an employee of AstraZeneca, any of its affiliates or partners, or the study center

No locations available

Arms	Assigned Interventions
Experimental: Aclidinium Bromide Two-week washout/run-in period [for patients on a long-acting muscarinic antagonist (LAMA)] followed by a maximum of 36-month double-blind treatment period.	Drug: Aclidinium Bromide 400 μg, twice per day, oral administration via a multi-dose dry-powder inhaler (DPI)
Placebo Comparator: Placebo Two-week washout/run-in period [for patients on a long-acting muscarinic antagonist (LAMA)] followed by a maximum of 36-month double-blind treatment period.	Drug: Placebo Dose matched placebo, twice per day, oral administration via a multi-dose dry-powder inhaler (DPI)

Documents available

Protocol
Download
Statistical Analysis Plan (SAP)
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Kenneth R. Chapman

GSK-CIHR Research Chair in Respiratory Health Care Delivery,