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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease COPD
• Intervention / Treatment: Drug: Glycopyrronium/Formoterol Fumarate; Drug: umeclidinium/vilanterol

• Study Type: Interventional
• Enrollment (Actual): 1119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Dupnitsa, Bulgaria, 2600
    • Research Site
  • Dupnitsa, Bulgaria, 2602
    • Research Site
  • Haskovo, Bulgaria, 6305
    • Research Site
  • Kozloduy, Bulgaria, 3320
    • Research Site
  • Pazardzhik, Bulgaria, 4400
    • Research Site
  • Petrich, Bulgaria, 2850
    • Research Site
  • Pleven, Bulgaria, 5800
    • Research Site
  • Plovdiv, Bulgaria, 4002
    • Research Site
  • Razlog, Bulgaria, 2760
    • Research Site
  • Ruse, Bulgaria, 7002
    • Research Site
  • Sliven, Bulgaria, 8800
    • Research Site
  • Smolyan, Bulgaria, 4700
    • Research Site
  • Sofia, Bulgaria, 1407
    • Research Site
  • Sofia, Bulgaria, 1233
    • Research Site
  • Sofia, Bulgaria, 1618
    • Research Site
  • Sofia, Bulgaria, 1002
    • Research Site
  • Sofia, Bulgaria, 1408
    • Research Site
  • Stara Zagora, Bulgaria, 6000
    • Research Site
  • Varna, Bulgaria, 9000
    • Research Site
  • Vidin, Bulgaria, 3700
    • Research Site
• Canada
  • Quebec, Canada, G1G 3Y8
    • Research Site
  • Quebec, Canada, G1V 4G5
    • Research Site
  • Quebec, Canada, G3K 2P8
    • Research Site
  • Alberta
    • Sherwood Park, Alberta, Canada, T8L 0N2
      • Research Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2V 4W3
      • Research Site
  • Nova Scotia
    • Truro, Nova Scotia, Canada, B2N 1L2
      • Research Site
  • Ontario
    • Burlington, Ontario, Canada, L7N 3V2
      • Research Site
    • Burlington, Ontario, Canada, L7M 4Y1
      • Research Site
    • Etobicoke, Ontario, Canada, M9W 4L6
      • Research Site
    • Windsor, Ontario, Canada, N8X 1T3
      • Research Site
    • Windsor, Ontario, Canada, N8X-5A6
      • Research Site
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 6S8
      • Research Site
    • Levis, Quebec, Canada, G6W 0M5
      • Research Site
    • St Charles Borromee, Quebec, Canada, J6E 2B4
      • Research Site
• France
  • Besancon Cedex, France, 25030
    • Research Site
  • Brest Cedex, France, 29609
    • Research Site
  • Lyon Cedex 04, France, 69317
    • Research Site
  • Montpellier, France, 34295
    • Research Site
  • Nantes Cedex 2, France, 44277
    • Research Site
  • Pessac, France, 33604
    • Research Site
  • Poitiers, France, 86021
    • Research Site
  • Reims, France, 51092
    • Research Site
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Research Site
  • Budapest, Hungary, 1135
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Debrecen, Hungary, H-4031
    • Research Site
  • Farkasgyepü, Hungary, 8582
    • Research Site
  • Hajdúnánás, Hungary, 4080
    • Research Site
  • Komló, Hungary, 7300
    • Research Site
  • Komárom, Hungary, 2900
    • Research Site
  • Miskolc, Hungary, 3529
    • Research Site
  • Püspökladány, Hungary, 4150
    • Research Site
  • Siófok, Hungary, 8600
    • Research Site
  • Szeged, Hungary, H-6722
    • Research Site
  • Szombathely, Hungary, 9700
    • Research Site
  • Vásárosnamény, Hungary, 4800
    • Research Site
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • Research Site
  • Barnaul, Russian Federation, 656038
    • Research Site
  • Chelyabinsk, Russian Federation, 454021
    • Research Site
  • Ekaterinburg, Russian Federation, 620028
    • Research Site
  • Izhevsk, Russian Federation, 426035
    • Research Site
  • Moscow, Russian Federation, 109544
    • Research Site
  • Novosibirsk, Russian Federation, 630051
    • Research Site
  • Penza, Russian Federation, 440026
    • Research Site
  • Penza, Russian Federation, 440067
    • Research Site
  • Ryazan, Russian Federation, 390005
    • Research Site
  • Saint Petersburg, Russian Federation, 197342
    • Research Site
  • Saint Petersburg, Russian Federation, 198260
    • Research Site
  • Saint Petersburg, Russian Federation, 191015
    • Research Site
  • Saint-Petersburg, Russian Federation, 194291
    • Research Site
  • Saint-Petersburg, Russian Federation, 196084
    • Research Site
  • Saint-Petersburg, Russian Federation, 191180
    • Research Site
  • Saratov, Russian Federation, 410012
    • Research Site
  • Smolensk, Russian Federation, 214006
    • Research Site
  • St. Petersburg, Russian Federation, 197022
    • Research Site
  • Tomsk, Russian Federation, 634050
    • Research Site
  • Ulyanovsk, Russian Federation, 432009
    • Research Site
• Ukraine
  • Chernivtsi, Ukraine, 58001
    • Research Site
  • Chernivtsi, Ukraine, 58000
    • Research Site
  • Ivano-Frankivsk, Ukraine, 76012
    • Research Site
  • Kharkiv, Ukraine, 61002
    • Research Site
  • Kharkiv, Ukraine, 61058
    • Research Site
  • Kharkiv, Ukraine, 61035
    • Research Site
  • Kyiv, Ukraine, 04107
    • Research Site
  • Kyiv, Ukraine, 03680
    • Research Site
  • Lutsk, Ukraine, 43000
    • Research Site
  • Lviv, Ukraine, 79066
    • Research Site
  • Odesa, Ukraine, 65025
    • Research Site
  • Poltava, Ukraine, 36040
    • Research Site
  • Vinnytsia, Ukraine, 21029
    • Research Site
  • Vinnytsia, Ukraine, 21001
    • Research Site
  • Zaporizhzhia, Ukraine, 69096
    • Research Site
• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Research Site
  • California
    • Escondido, California, United States, 92025
      • Research Site
    • Sacramento, California, United States, 95821
      • Research Site
  • Florida
    • Hollywood, Florida, United States, 33021
      • Research Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Research Site
    • Rincon, Georgia, United States, 31326
      • Research Site
  • Michigan
    • Farmington Hills, Michigan, United States, 48336
      • Research Site
  • New York
    • Bronx, New York, United States, 10455
      • Research Site
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Research Site
  • Ohio
    • Dublin, Ohio, United States, 43016
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15243
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Research Site
    • Spartanburg, South Carolina, United States, 29303
      • Research Site
  • Texas
    • Sherman, Texas, United States, 75092
      • Research Site
    • Tomball, Texas, United States, 77375
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 93 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; glycopyrronium/formoterol fumarate 7.2/4.8 μg per actuation, twice daily	Drug: Glycopyrronium/Formoterol Fumarate; Metered dose inhaler (MDI), contains glycopyrronium/formoterol fumarate fixed-dose combination 7.2/4.8 μg per actuation
Active Comparator: Active comparator; umeclidinium/vilanterol 62.5/ 25μg per inhalation, once daily	Drug: umeclidinium/vilanterol; Dry powder inhaler (DPI), Each metered dose contains umeclidinium/vilanterol 62.5/ 25μg fixed-dose combination per inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel International Ltd; Cognizant Technology Solution; Center for Information & Study on Clinical Research Participation (CISCRP); eResearchTechnology; QuintilesIMS Limited; Corporate Translations Inc

Publications and helpful links

General Publications

• Maltais F, Ferguson GT, Feldman GJ, Deslee G, Bourdin A, Fjallbrant H, Siwek-Posluszna A, Jenkins MA, Martin UJ. A Randomized, Double-Blind, Double-Dummy Study of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Relative to Umeclidinium/Vilanterol Dry Powder Inhaler in COPD. Adv Ther. 2019 Sep;36(9):2434-2449. doi: 10.1007/s12325-019-01015-3. Epub 2019 Jul 2.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2017
• Primary Completion (Actual): May 4, 2018
• Study Completion (Actual): May 4, 2018

Study Registration Dates

• First Submitted: May 19, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): May 22, 2019
• Last Update Submitted That Met QC Criteria: April 30, 2019
• Last Verified: April 1, 2019

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; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Glycopyrrolate; Formoterol Fumarate
• Other Study ID Numbers: D5970C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No