Welcome to this UK AstraZeneca produced and funded website
This website is intended for UK Healthcare Professionals only.
The website contains both promotional and non-promotional content.
If you are a patient or a carer of a patient prescribed an AstraZeneca product, please visit myazmed.co.uk
For any other UK residents please visit astrazeneca.co.uk
This website is intended for UK Healthcare Professionals only. Other UK residents please visit astrazeneca.co.uk
| ETHOS2 – Exacerbation study | KRONOS3 - Lung function study | |
|---|---|---|
| Study Design | Phase III, randomised, double-blind, multicentre, parallel arm efficacy (exacerbation rate) and safety study | Phase III, randomised, double-blind, parallel arm with open-label ICS/LABA (BFF) DPI arm efficacy (lung function change) and safety study |
| Study size | 8,588 randomised patients | 1,902 randomised patients |
| Study duration | 52 weeks | 24 weeks |
| Patient population difference between ETHOS and KRONOS | 100% of patients had ≥1 moderate or severe COPD exacerbation(s) in a year prior to screening | 74% of patients did NOT have a history of exacerbations in a year prior to screening |
| Selected inclusion criteria* | Post-bronchodilator FEV1 <50% of predicted normal must have a documented history of ≥1 moderate or severe COPD exacerbation in the 12 months prior to screening | No requirement for history of exacerbations in a year prior to screening |
| Post-bronchodilator FEV1 ≥50% of predicted normal must have a documented history of ≥2 moderate exacerbations or a documented history of ≥1 severe COPD exacerbation in the 12 months prior to screening | ||
| FEV1 must be ≥25% to <65% predicted normal value | Post-bronchodilator FEV1 must be ≥25% to <80% | |
| 40-80 years of age Established clinical history of COPD and post-BD FEV1/FVC ratio <0.70 Current or former smokers with a history of at least 10 pack-years of cigarette smoking Symptomatic (CAT ≥10) Two or more inhaled maintenance therapies for the management of their COPD for at least 6 weeks prior to Screening, Scheduled SABA and/or SAMA were considered inhaled maintenance therapies. | ||
| Selected exclusion criteria* | Current diagnosis of asthma or diagnosis of any active respiratory disease or condition other than COPD | |
| Study arms (number of randomised patients) |
|
|
| Selected primary endpoints* | Rate of moderate or severe COPD exacerbations | FEV1 area under the curve from 0 to 4 hours (AUC0-4) over 24 weeks Change from baseline in morning pre-dose through FEV1 over 24 weeks |
| Selected secondary endpoints* |
|
|
| *Here are presented core inclusion and exclusion criteria as well as UK applicable selected endpoints. Different endpoints are due to different regulatory requirements in different territories. Full list of criteria and endpoints is available in study protocols.4,5 **ICS/LABA (BFF) AEROSPHERE pMDI is not licensed in the UK and is confirmed as non-inferior to the UK licensed ICS/LABA (BFF) DPI by KRONOS study. †BGF160 pMDI (budesonide 80μg / glycopyrronium 7.2μg / formoterol 5μg per actuation) is experimental and not licensed in the UK therefore related outcomes have not been presented here. ††ICS/LABA (BFF) DPI served to validate non-inferiority of ICS/LABA (BFF) AEROSPHERE pMDI therefore related outcomes have not been presented here; it is licensed in the UK as Symbicort Turbohaler 200/6 Inhalation powder. | ||
Moderate exacerbations were defined as events requiring the use of OCS/systemic corticosteroids and/or antibiotics for at least 3 days.2-5
Severe exacerbations were defined as events resulting in patient COPD-related hospitalisation or COPD-related death.2-5
ICS/LABA (BFF) AEROSPHERE pMDI is not licensed in the UK and is confirmed as non-inferior to the UK licensed ICS/LABA (BFF) DPI by KRONOS study. All treatments were administered two inhalations BID
24%
Annual rates 1.08 vs 1.42; RR 0.76, 95% CI 0.69 to 0.83, p<0.001; ARR 0.34 exacerbations per patient per year. NNT 36
13%
Annual rates 1.08 vs 1.24; RR 0.87, 95% CI 0.79 to 0.95, p=0.003; ARR 0.16 exacerbations per patient per year. NNT 66
16%
Annual rates 0.13 vs 0.15; RR 0.84, 95% CI 0.69 to 1.03, p=0.09; not significant ARR 0.02 exacerbations per patient per year6
20%
Annual rates 0.13 vs 0.16; RR 0.80, 95% CI 0.66 to 0.97, p=0.02; ARR 0.03 exacerbations per patient per year. NNT 336
HR 0.51; 95% CI 0.33 to 0.80; unadjusted p=0.00357
HR 0.72; 95% CI 0.44 to 1.16; p=0.1721 not significant7
ICS/LABA (BFF) AEROSPHERE pMDI is not licensed in the UK and is confirmed as non-inferior to the UK licensed ICS/LABA (BFF) DPI by KRONOS study. All treatments were administered two inhalations BID
95% CI: 4 to 39: p=0.0139
95% CI: 52 to 95: p<0.0001
95% CI: -6 to 38: p=0.1448 not significant
95% CI: 77 to 131: p<0.0001
Annual rates 0.46 vs 0.95; RR 0.48, 95% CI 0.37 to 0.64, p<0.0001; ARR 0.49 exacerbations per patient per year3 NNT 26
18% reduction vs ICS/LABA pMDI annual rates 0.46 vs 0.56; ARR 0.1; RR 0.82, 95% CI 0.58 – 1.17; p=0.2792 (not significant)3
ICS/LAMA/LABA (BGF) AEROSPHERE pMDI – budesonide 160μg / glycopyrronium 7.2 μg / formoterol 5 μg per actuation using AEROSPHERE technology in a pressurised metered dose inhaler; licensed in the UK as TRIXEO AEROSPHERE pMDI
LAMA/LABA (GFF) AEROSPHERE pMDI - glycopyrronium 7.2 μg / formoterol 5 μg per actuation using AEROSPHERE technology in a pressurised metered dose inhaler; licensed in the UK as BEVESPI AEROSPHERE pMDI
ICS/LABA (BFF) AEROSPHERE pMDI - budesonide 160μg / formoterol 5 μg per actuation using AEROSPHERE technology in a pressurised metered dose inhaler is not licensed in the UK and is confirmed as non-inferior to the UK licensed ICS/LABA (BFF) DPI by KRONOS study
ARR, absolute rate reduction; AUC, area under the curve; BGF160, budesonide 80μg / glycopyrronium 7.2μg / formoterol 5μg per actuation; BID, two times a day; CI, confidence interval; COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; FEV1, forced expiratory volume in the first second; HR, hazard ratio ICS, inhaled corticosteroid; LABA, long-acting beta2 agonist; LAMA, long-acting muscarinic antagonist; NNT, number needed to treat; OCS, oral corticosteroid; pMDI, pressurised metered dose inhaler; RR, rate ratio; SABA, short-acting beta2 agonist; SAMA, short-acting muscarinic antagonist; SGRQ, St George's Respiratory Questionnaire; CAT, COPD assessment test; FVC, forced vital capacity; FEV1/FVC, ratio of the forced expiratory volume in the first one second to the forced vital capacity of the lungs; BD, bronchodilator; n, number of patients.
GB-56993 | November 2024
TRIXEO and AEROSPHERE are registered trademarks of the AstraZeneca group of companies.
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to AstraZeneca by visiting https://contactazmedical.astrazeneca.com/ or by calling 0800 783 0033.
This website was created for UK HCPs and has been designed to provide information to educate, empower and enable them in the great work they are doing for patients across a range of therapy areas. This website is intended for doctors, nurses, and pharmacists in the UK. Other UK residents please visit astrazeneca.co.uk.
