Efficacy and Safety of Glycopyrronium/Formoterol Fumarate Fixed-dose Combination Relative to Umeclidinium/Vilanterol Fixed-dose Combination Over 24 Weeks in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease COPD Clinical Trial

— AERISTO  

Official title:

A Randomised, Double-Blind, Double-Dummy, Multicentre, Parallel Group Study to Assess the Efficacy and Safety of Glycopyrronium/Formoterol Fumarate Fixed-dose Combination Relative to Umeclidinium/Vilanterol Fixed-dose Combination Over 24 Weeks in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (AERISTO)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03162055
• Other study ID #: D5970C00002
• Status: Completed
• Phase: Phase 3
• Start date: May 25, 2017
• Est. completion date: May 4, 2018

Study information

• Verified date: April 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase IIIb randomised, double-blind, double-dummy, multicentre, parallel group, 24 week study to assess the efficacy and safety of Glycopyrronium/Formoterol Fumarate (GFF) fixed-dose combination 7.2/4.8 μg 2 inhalations twice daily compared to Umeclidinium/Vilanterol (UV) 62.5/25 μg fixed-dose combination 1 inhalation once daily in Patients with moderate to very severe COPD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1119
• Est. completion date: May 4, 2018
• Est. primary completion date: May 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 95 Years

Eligibility

Inclusion criteria:

• Age 40-95 years at screening

• Current or former smoker with a history of at least 10 pack-years of cigarette smoking

• Current clinical diagnosis of COPD, with COPD symptoms > 1 year prior to screening, as defined by GOLD criteria or other current guidelines

• COPD Severity defined by FEV1/FVC ratio <0.70 and FEV1 <80% of predicted normal value at screening and at randomisation

• COPD treatment with rescue medication only, or stable dose of maintenance monotherapy (LAMA, LABA or ICS), or stable dose of double maintenance therapy (LAMA/LABA or ICS/LABA), for one month prior to screening

• COPD Assessment Test (CAT) score =10 at randomisation

• Documentation of a chest x-ray (as per local practice) or computed tomography (CT) within 6 months prior to screening, with no clinically significant pulmonary abnormalities other than related to COPD

Exclusion criteria:

• Respiratory disease other than COPD, including:

• Current diagnosis of asthma

• Alpha-1 Antitrypsin Deficiency as the cause of COPD

• Other respiratory disorders and conditions as listed in the protocol

• Severe COPD exacerbation (resulting in hospitalisation) not resolved within 8 weeks prior to screening, or moderate exacerbation not resolved within 4 weeks, or during screening

• Pneumonia or lower respiratory tract infection that required antibiotics within 8 weeks prior to screening, or during screening.

• Significant diseases or conditions other than COPD which may put the patient at risk, or influence the results of the study or the patient's ability to participate, including cardiac disease, advanced renal disease, and cancer that has not been in complete remission for at least 5 years.

• Patients who have needed additions or alterations to their usual maintenance therapy for COPD due to worsening symptoms within 1 month prior to and during screening

• Treatment with depot corticosteroids within 6 weeks, or other systemic corticosteroids within 4 weeks, prior to screening. (Patients maintained on an equivalent of 5 mg prednisone per day for at least 3 months prior to screening are allowed.)

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease COPD
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Glycopyrronium/Formoterol Fumarate
Metered dose inhaler (MDI), contains glycopyrronium/formoterol fumarate fixed-dose combination 7.2/4.8 µg per actuation
• umeclidinium/vilanterol
Dry powder inhaler (DPI), Each metered dose contains umeclidinium/vilanterol 62.5/ 25µg fixed-dose combination per inhalation

Locations

Country	Name	City	State
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Petrich
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Razlog
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Smolyan
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Vidin
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Etobicoke	Ontario
Canada	Research Site	Gatineau	Quebec
Canada	Research Site	Levis	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Truro	Nova Scotia
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Winnipeg	Manitoba
France	Research Site	Besancon Cedex
France	Research Site	Brest Cedex
France	Research Site	Lyon Cedex 04
France	Research Site	Montpellier
France	Research Site	Nantes Cedex 2
France	Research Site	Pessac
France	Research Site	Poitiers
France	Research Site	Reims
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Debrecen
Hungary	Research Site	Farkasgyepü
Hungary	Research Site	Hajdúnánás
Hungary	Research Site	Komárom
Hungary	Research Site	Komló
Hungary	Research Site	Miskolc
Hungary	Research Site	Püspökladány
Hungary	Research Site	Siófok
Hungary	Research Site	Szeged
Hungary	Research Site	Szombathely
Hungary	Research Site	Vásárosnamény
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Ulyanovsk
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Poltava
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhia
United States	Research Site	Bronx	New York
United States	Research Site	Dublin	Ohio
United States	Research Site	Escondido	California
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hollywood	Florida
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Rincon	Georgia
United States	Research Site	Sacramento	California
United States	Research Site	Sherman	Texas
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Tempe	Arizona
United States	Research Site	Tomball	Texas

Sponsors (7)

Lead Sponsor	Collaborator
AstraZeneca	Center for Information & Study on Clinical Research Participation (CISCRP), Cognizant Technology Solution, Corporate Translations Inc, eResearchTechnology, Parexel International Ltd, QuintilesIMS Limited

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  France,  Hungary,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean Change From Baseline in Night-Time Symptoms of COPD Instrument (NiSCI) Over 24 Weeks	Change from baseline in the 6-item NiSCI Symptom Severity Score was derived by averaging the responses from a participant on the 6 item-level symptom scores (scored on a 4-point scale from 1 to 4, whereas 1= mild and 4= very severe). The NiSCI collected data about the frequency and severity of night-time symptoms and the impact of COPD symptoms on night-time awakenings in participants with COPD. Participants completed a daily ePRO questionnaire for their COPD symptoms. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1).	From Baseline (Day -7) up to 24 weeks
Other	Mean Change From Baseline in Daily Rescue (Albuterol/Salbutamol MDI) Use Over 24 Weeks	The number of inhalations of rescue albuterol/salbutamol MDI was recorded in the participant ePRO in the morning and evening. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1). a/s = albuterol/salbutamol.	From Baseline (Day -7) up to 24 weeks
Other	Mean Change From Baseline in COPD Assessment Test (CAT) Score Over 24 Weeks	The CAT is used to quantify the impact of COPD symptoms on health status. The CAT has a scoring range of 0-40, and it is calculated as the sum of the responses given for each of the 8 items (scored on a 6-point scale from 0 to 5), with higher scores indicating a higher impact of COPD symptoms on health status. If the response to 1 of the 8 items is missing, the missing item was considered equal to the average of the 7 non-missing items for that participant. If more than 1 item is missing the score was considered missing. Baseline is defined as the latest assessment within 7 days before or at randomization (Day 1).	From Baseline (Day -7 or 1) up to 24 weeks
Primary	Mean Change From Baseline in Morning Pre-dose Trough Forced Expiratory Volume in 1 Second (FEV1) Over 24 Weeks	To assess the effects of GFF relative to UV on lung function as measured by change from baseline in morning pre-dose trough FEV1 is defined as the average of the -60 and -30 minute pre-dose values at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1). BR a/s = bronchodilator responsiveness to albuterol/salbutamol.	From Baseline (Day 1) up to 24 weeks
Primary	Mean Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks in PP Analysis Set Population	To assess the effects of GFF relative to UV on lung function in PP analysis set population as measured by peak change from baseline in FEV1 is defined as the maximum of the FEV1 assessments within the 2 hours post-dosing time windows at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1).	From Baseline (Day 1) up to 24 weeks
Primary	Mean Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks in FAS Population	To assess the effects of GFF relative to UV on lung function in FAS population as measured by peak change from baseline in FEV1 is defined as the maximum of the FEV1 assessments within the 2 hours post-dosing time windows at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1).	From Baseline (Day 1) up to 24 weeks
Secondary	Percentage of Participants With Increase of FEV1 of >=100 mL From Baseline at 5 Minutes Post-dosing on Day 1	The percentage of participants with an increase in FEV1 of >=100 mL from baseline at 5 minutes post-dosing on Day 1 was determined to assess the early onset of action. Baseline is defined as the average of available evaluable -60 and -30 minute pre-dose assessments conducted at randomization (Day 1). Only data assigned to the 5 minute window was used to determine response. Participants with missing data were considered non-responders for the analysis.	5 minutes post-dose on Day 1
Secondary	Mean Peak Change From Baseline in Inspiratory Capacity (IC) Within 2 Hours Post-dosing Over 24 Weeks	Peak change from baseline in IC is defined as the maximum of the IC assessments within the 2 hours post-dosing time windows at each visit minus baseline. Baseline is defined as the average of available evaluable -60 and -30 minute pre-dose assessments conducted at randomization (Day 1).	From Baseline (Day 1) up to 24 weeks
Secondary	Mean Transition Dyspnea Index (TDI) Focal Score Over 24 Weeks	The baseline dyspnea index (BDI) and TDI consist of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these 3 components were rated in 5 grades from 0 (very severe) to 4 (no impairment), and were summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea were rated for each component by 7 grades from -3 (major deterioration) to +3 (major improvement), and were added to form a TDI focal score from -9 to +9. Baseline is defined as the latest BDI assessment within 7 days before or at randomization (Day 1).	From Baseline (Day -7 or 1) up to 24 weeks
Secondary	Mean Change From Baseline in Early Morning Symptoms of COPD Instrument (EMSCI) Over 24 Weeks	Change from baseline in the 6-item EMSCI Symptom Severity Score was derived by averaging the responses from a participant on the 6 item-level symptom scores (scored on a 4-point scale from 1 to 4, whereas 1= mild and 4= very severe). The EMSCI collected data about the frequency and severity of early morning symptoms and the impact of COPD symptoms on early morning activity in participants with COPD. Participants completed a daily electronic patient-reported outcome (ePRO) questionnaire for their COPD symptoms. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1). TI = Time interval.	From Baseline (Day -7) up to 24 weeks