Efficacy and Safety of Three Doses of Aclidinium Bromide Compared to Placebo and to an Active Comparator in Chronic Obstructive Pulmonary Disease (COPD) Patients.

Efficacy and Safety of Three Doses of Aclidinium Bromide Compared to Placebo and to an Active Comparator All Administered Twice Daily by Inhalation in Patients With Stable Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD).

The present trial is conducted to further assess the efficacy by means of serial spirometry, safety and tolerability of three doses of aclidinium bromide administered twice a day compared to previously approved BID drug, formoterol 12 µg, and placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).after 7 days on treatment. Every treatment period is 7-days long and there is a 5 to 7-days wash-out period in between them. The trial starts with a run in phase of 11 to 17-days duration and it ends up with a follow up contact 14-days after last treatment dose.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Aclidinium bromide 100 μg bid; Drug: Aclidinium bromide 200 μg bid; Drug: Aclidininum bromide 400 μg bid; Drug: Placebo; Drug: Formoterol 12 μg bid

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, B-9000
    • Almirall Investigational Sites#1
• Germany
  • Berlín, Germany, 10117
    • Almirall Investigational Sites#3
  • Berlín, Germany, 13125
    • Almirall Investigational Sites#4
  • Berlín, Germany, 14050
    • Almirall Investigational Sites#9
  • Frankfurt, Germany, 60596
    • Almirall Investigational Sites#8
  • Groβhansdorf, Germany, 22927
    • Almirall Investigational Sites#1
  • Hamburg, Germany, 20249
    • Almirall Investigational Sites#5
  • Hannover, Germany, 30159
    • Almirall Investigational Sites#7
  • Hannover, Germany, 30625
    • Almirall Investigational Sites#2
  • Schwerin, Germany, 19055
    • Almirall Investigational Sites#6
  • Wiesbaden, Germany, 65187
    • Almirall Investigational Sites#10

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and non-pregnant, non-lactating females aged ≥ 40.
2. Patients with a clinical diagnosis of stable moderate to severe COPD, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines: (http://www.goldcopd.com) and stable airway obstruction. Post-salbutamol FEV1/FVC < 70% at Screening Visit (Visit 1) (i.e., 100xpost-salbutamol FEV1/FVC <70%).
3. Current, or ex-cigarette smoker with a smoking history of at least 10 pack-years.
4. Patient whose FEV1 at the Screening Visit measured between 10-15 minutes post inhalation of salbutamol is 30% < FEV1 <80% of the predicted normal value (i.e., 100 x Post-salbutamol FEV1/ Predicted FEV1 must be < 80% and ≥ 30%).
5. Female patients at least 1 year post-menopausal, surgically sterile (defined as having a hysterectomy or tubal ligation), or practicing a medically approved and highly effective method of contraception.
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. History or current diagnosis of asthma.
2. Clinically significant respiratory conditions other than COPD at the time of Inform Consent signature
3. Hospitalisation due to COPD exacerbation within the previous 3 months.
4. Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract) within the previous 6 weeks.
5. Clinically significant cardiovascular conditions
6. Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction.
7. Presence of narrow-angle glaucoma.
8. QTcB) above 470 milliseconds in the ECG performed at Screening Visit,
9. Patient who does not maintain regular day/night, waking/sleeping cycles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aclidinium bromide 100 μg bid; Aclidininum bromide 100 μg twice daily by inhalation	Drug: Aclidinium bromide 100 μg bid; Aclidinium bromide 100 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days
Experimental: Aclidininum bromide 200 μg bid; Aclidininum bromide 200 μg twice daily by inhalation	Drug: Aclidinium bromide 200 μg bid; Aclidinium bromide 200 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days
Experimental: Aclidininum bromide 400 μg bid; Aclidininum bromide 400 μg twice daily by inhalation	Drug: Aclidininum bromide 400 μg bid; Aclidinium bromide 400 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days
Placebo Comparator: Placebo; Placebo twice-daily by inhalation	Drug: Placebo; Placebo via inhalation in the morning and evening for 7 days
Active Comparator: Formoterol 12 μg bid; Formoterol 12 μg twice daily by inhalation	Drug: Formoterol 12 μg bid; Formoterol 12 μg twice-daily via inhalation by Aerolizer® dry powder inhaler: 1 puff in the morning and evening for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment	Day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment	Day 7
Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment	Day 7
Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment	Day 7

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Singh D, Magnussen H, Kirsten A, Mindt S, Caracta C, Seoane B, Jarreta D, Garcia Gil E. A randomised, placebo- and active-controlled dose-finding study of aclidinium bromide administered twice a day in COPD patients. Pulm Pharmacol Ther. 2012 Jun;25(3):248-53. doi: 10.1016/j.pupt.2012.03.008. Epub 2012 Apr 4. Erratum In: Pulm Pharmacol Ther. 2013 Apr;26(2):305.

Helpful Links

• Almirall Corporate Website
• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: May 7, 2010
• First Submitted That Met QC Criteria: May 7, 2010
• First Posted (Estimate): May 10, 2010

Study Record Updates

• Last Update Posted (Estimate): January 9, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; 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: M/34273/29; LAS29