Clinical trial NCT02153489: A Double-blind, Placebo-controlled, Crossover Study to Assess the Effect of Aclidinium Bromide 400 μg Bid on COPD Symptoms and Sleep Quality After 3 Weeks of Treatment in Patients With Stable Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Pilot, Double-blind, Placebo-controlled, 2-period Crossover Study to Assess the Effect of Aclidinium Bromide 400 μg Bid on COPD Symptoms and Sleep Quality After 3 Weeks of Treatment in Patients With Stable Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-06-03
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of aclidinium bromide compared with placebo in improving dilatation of the airways (bronchodilation), symptoms of chronic obstructive pulmonary disease (COPD), sleep quality and physical activity after 3 weeks of treatment with aclidinium bromide 400 μg administered twice daily in patients with stable moderate-and-severe COPD.


Eligibility criteria: Inclusion Criteria:

* Adult male or non-pregnant, non-lactating female aged ≥40 years. Women of childbearing potential will follow specific study requirements (negative serum pregnancy test at the Screening Visit and are using, over the last two months before the Screening Visit, at least one medically approved and highly effective method of birth control
* Current or ex-cigarette smoker (patients who quit smoking more than 6 months prior to the Screening Visit), with a smoking history of at least 10 pack-years.
* Patients with a clinical diagnosis of chronic obstructive pulmonary disease (COPD) according to GOLD guidelines 2013, with a post bronchodilator FEV1 \<80%, and FEV1 ≥ 40% at Screening Visit
* Patients must be able to perform repeatable pulmonary function testing for FEV1 according to American Thoracic Society \[ATS\]/European Respiratory Society \[ERS\] 2005 criteria at Screening Visit
* Patients who are eligible and able to participate in the study and who consents to do so in writing after the purpose and nature of the investigation have been explained

Exclusion Criteria:

* History or current diagnosis of asthma
* Patients with moderate to severe sleep apnoea assessed at screening
* Patients who develop a respiratory tract infection or COPD exacerbation within 6 weeks (or 3 months if hospitalisation was required) before the Screening Visit (Visit 1) or during the run-in period
* Clinically significant respiratory conditions
* Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated hypertension
* Patients who may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to the Screening Visit
* Use of long-term oxygen therapy (15 hours/day)
* Patients who does not maintain regular day/night, waking/sleeping cycles including night shift workers
* Clinically significant cardiovascular conditions
* QTc \>470 milliseconds in the manual ECG reading performed at Screening Visit
* Patients with clinically relevant abnormalities in the opinion of the investigator at the Screening Visit (Visit 1) in the results of the clinical laboratory tests, ECG parameters or in the physical examination)
* Patients with a history of hypersensitivity reaction to inhaled anticholinergics, long and short acting β2-agonists, sympathomimetic amines, or inhaled medication or any component there of (including report of paradoxical bronchospasm)
* Patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy
* Patients with known non-controlled history of human immunodeficiency virus (HIV) infection and/or active hepatitis
* 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
* Patients with any other serious or uncontrolled physical or mental dysfunction, or moderate-to-severe depression, as confirmed by Beck Depression Inventory (BDI-II) total score \>28.
* Patients with a history (within 2 years prior to the Screening Visit) of drug and/or alcohol abuse that may prevent study compliance based on investigator judgment
* Patients unlikely to be cooperative or that can't comply with the study procedures.
* Patients treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to the Screening Visit
* Patients who intends to use any concomitant medication not permitted by this protocol or who have not undergone the required stabilization periods for prohibited medication
* Any other conditions that, in the investigator's opinion, might indicate the patient to be unsuitable for the study

Primary outcomes:
measure: Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-24hr
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 11, 12, 12.5, 13, 14, 15, 16, 19, 22, 23, and 24 hours at Week 3 of treatment
Secondary outcomes:
Other outcomes:
measure: Change From Baseline in Morning Trough FEV1
timeFrame: Week 3 of treatment
measure: Change From Baseline in Peak FEV1
timeFrame: Week 3 of treatment
measure: Change From Baseline in Normalized FEV1 AUC0-12hr
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 11 and 12 hours at Week 3 of treatment
measure: Change From Baseline in Normalized FEV1 AUC12-24hr
timeFrame: 12, 12.5, 13, 14, 15, 16, 19, 22, 23, and 24 hours at Week 3 of treatment
measure: Change From Baseline in the Average Rating of Overall Early Morning COPD Symptom Severity
timeFrame: Week 3 of treatment
measure: Change From Baseline in the Average Rating of Overall Evening COPD Symptom Severity
timeFrame: Week 3 of treatment
measure: Change From Baseline in the Average Rating of Overall Night-time COPD Symptom Severity
timeFrame: Week 3 of treatment
measure: Change From Baseline in the Average Rating of COPD Symptoms Limiting Early Morning Activities
timeFrame: Week 3 of treatment
measure: Change From Baseline in the Average Rating of COPD Symptoms Limiting Evening Activities
timeFrame: Week 3 of treatment
measure: Change From Baseline in Apnea-hypopnea Index (AHI) Per Hour of Total Sleep Time
timeFrame: Week 3 of treatment
measure: Change From Baseline in Oxygen Desaturation Index (ODI) Per Hour of Total Sleep Time
timeFrame: Week 3 of treatment
measure: Change From Baseline in Proportion of Sleep Stage REM as a Percentage of Total Sleep Time
timeFrame: Week 3 of treatment
measure: Change From Baseline in Sleep Efficiency
timeFrame: Week 3 of treatment
measure: Change From Baseline in Total Sleep Time
timeFrame: Week 3 of treatment
measure: Change From Baseline in Duration of at Least Moderate Activity
timeFrame: Week 3 of treatment
measure: Change From Baseline in Number of Steps Per Day
timeFrame: Week 3 of treatment
Locations:
city: Grosshansdorf
country: Germany
facility: Pulmonary Research Institute at the Lung Clinic Grosshansdorf
city: Immenhausen
country: Germany
facility: Pneumologische Lehrklinik der Universitätsmedizin Göttingen
Study officials:
affiliation: AstraZeneca Barcelona
name: Anna Ribera, PhD
role: STUDY_DIRECTOR
References:
citation: Magnussen H, Arzt M, Andreas S, Plate T, Ribera A, Seoane B, Watz H, Kirsten AM. Aclidinium bromide improves symptoms and sleep quality in COPD: a pilot study. Eur Respir J. 2017 Jun 22;49(6):1700485. doi: 10.1183/13993003.00485-2017. Print 2017 Jun. No abstract available.