Efficacy and Safety of Two Fixed Dose Combinations of Aclidinium Bromide With Formoterol Fumarate (ALIGHT-COPD)

Efficacy, Safety and Tolerability of Two Fixed-Dose Combinations of Aclidinium Bromide With Two Doses of Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo All Administered Twice Daily in Stable, Moderate to Severe Chronic Obstructive Pulmonary Disease Patients.

The purpose of this multicenter, dose-ranging study is to compare two Fixed-Dose Combinations of aclidinium bromide and formoterol fumarate with placebo, aclidinium bromide and formoterol fumarate, all administered BID in patients with stable, moderate to severe COPD.

Every treatment period is 14-days long and there is a 7-days wash-out period in between them. The trial starts with a run in phase of 10 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
• Intervention / Treatment: Drug: Formoterol 12 μg; Drug: Placebo; Drug: Aclidinium 200 μg / formoterol 12 μg; Drug: Aclidinium 200 μg / Formoterol 6 μg; Drug: Aclidinium 200 μg

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Bucuresti, Czech Republic
    • Research Site
  • Constanta, Czech Republic
    • Research Site
  • Iasi, Czech Republic
    • Research Site
  • Tg Mures, Czech Republic
    • Research Site
• Romania
  • Bucuresti, Romania
    • Research Site
  • Cluj Napoca, Romania
    • Research Site
  • Deva, Romania
    • Research Site
  • Iasi, Romania
    • Research Site
  • Oradea, Romania
    • Research Site
  • Timisoara, Romania
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 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 aged between 40 and 80 years old, both inclusive.
2. Patient with a clinical diagnosis of stable moderate to severe COPD according to the GOLD classification
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 400 mcg 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. Patient whose FEV1/FVC at the Screening Visit measured between 10-15 minutes post inhalation of 400 mcg of salbutamol is < 70% (i.e., 100 x Post-salbutamol FEV1 /FVC < 70%).
6. Patient who is eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained.
7. Patient whose COPD symptoms and FEV1 values at the time of randomisation are stable compared to the Screening Visit, according to the investigator's medical judgment

Exclusion Criteria:

1. History or current diagnosis of asthma or exercise-induced bronchospasm.
2. Clinically significant respiratory conditions 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. Patient who has a resting systolic blood pressure ≥ 200 mmHg, a resting diastolic blood pressure ≥ 120 mmHg or a resting heart rate ≥ 105 bpm at screening visit.
6. Clinically significant cardiovascular conditions
7. Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction.
8. Presence of narrow-angle glaucoma.
9. QTc [calculated according to Bazett's formulae (QTc=QT/RR1/2) above 470 milliseconds in the ECG performed at Screening Visit,
10. 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
Placebo Comparator: Placebo; Placebo twice daily	Drug: Placebo; Placebo control twice daily
Active Comparator: Formoterol 12 μg; Formoterol fumarate 12 μg twice daily	Drug: Formoterol 12 μg; Formoterol fumarate 12 μg twice daily
Experimental: Aclidinium 200 μg / formoterol 12 μg; Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) twice daily	Drug: Aclidinium 200 μg / formoterol 12 μg; Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) twice daily
Experimental: Aclidinium 200 μg / formoterol 6 μg; Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) twice daily	Drug: Aclidinium 200 μg / Formoterol 6 μg; Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) twice daily
Experimental: Aclidinium 200 μg; Aclidinium bromide 200 μg twice daily	Drug: Aclidinium 200 μg; Aclidinium bromide 200 μg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Normalized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) After Morning Study Drug Administration at Day 14	FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose	0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Morning Pre-dose FEV1 at Day 14	FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes	Day 14
Change From Baseline in Morning Peak FEV1 at Day 14	FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose	0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Almirall Corporate Website
• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: March 1, 2010
• First Submitted That Met QC Criteria: March 1, 2010
• First Posted (Estimate): March 2, 2010

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 5, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Chronic; Emphysema; Bronchitis
• 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; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate
• Other Study ID Numbers: M/40464/26