An Efficacy and Safety Study of Mitiperstat (AZD4831) (MPO Inhibitor) vs Placebo in the Treatment of Moderate to Severe COPD.

COPDCompEx is a composite endpoint of exacerbations and events defined from participant e-Diaries and peak expiratory flow (PEF). COPDCompEx defined exacerbations included episodes leading to one or more of the following: hospitalization, emergency room visit, treatment with systemic corticosteroids (injected and/or oral), or treatment with antibiotics. Diary COPDCompEx events are defined by threshold and slope criteria being met for \>= 2 consecutive days using the following diary and home spirometry variables: overall symptom rating, night-time awakenings due to symptoms, reliever medication use, PEF. COPDCompEx also includes patient withdrawals for treatment failure.

Time frame: From baseline to up to 24 weeks

Population: Full Analysis Set (FAS) included all randomised participants who received at least one dose of study intervention. 'While on treatment' estimand strategy was followed, which means that if an intercurrent event occurs all subsequent data for that subject was excluded from the evaluation.

COPD Assessment Test (CAT) is designed to measure how COPD impacts on a patient's daily life and how this might change over time. It consists of 8 questions that ask the patient to rate items relating to symptoms and impact on quality of life (such as normal activity and sleep). Each question is performed on a 5-point Likert scale from 0 (no symptoms/no impact) to 5 (severe symptoms/impact). The CAT will be completed by participants at on-site visits using the e-Diary.

Time frame: From baseline to Week 12

Population: Full Analysis Set (FAS) included all randomised participants who received at least one dose of study intervention. 'While on treatment' estimand strategy was followed, which means that if an intercurrent event occurs all subsequent data for that subject was excluded from the evaluation.

Change from baseline to Week 12 and week 24 in cough Visual Analogue Scale (VAS) score is reported. Participants were asked to complete a cough severity VAS (100-point linear scale marked with a horizontal line by the participant, with 0 representing ''no cough'' and 100 representing worst cough) that measured subjective assessment by the participant of the prior 24 hrs for severity of cough symptoms. It was completed each evening in the eDiary.

Time frame: From baseline to week 12 and week 24

Population: Full Analysis Set (FAS) included all randomised participants who received at least one dose of study intervention. 'While on treatment' estimand strategy was followed, which means that if an intercurrent event occurs all subsequent data for that subject was excluded from the evaluation.

Change from baseline in EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) which is a 14-item ePRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. It has a theoretical range of 0 to 100, with higher values indicating a more severe condition. The EXACT will be performed at on-site visits using the e-Diary.

Time frame: From baseline to week 12 and week 24

Population: Full Analysis Set (FAS) included all randomised participants who received at least one dose of study intervention. 'While on treatment' estimand strategy was followed, which means that if an intercurrent event occurs all subsequent data for that subject was excluded from the evaluation.

Change from baseline to Week 12 and week 24 in mean Breathlessness, Cough and Sputum Scale (BCSS) score is reported. The BCSS was a 3-item daily diary that assesses the severity of the 3 symptoms: breathlessness, sputum, and cough, each on a 5-point Likert scale ranging from 0 (no symptoms) to 4 (severe symptoms). Item scores were summed to yield a total score ranging from 0 to 12; wherein higher total score indicated more severe symptoms. The BCSS was captured each evening via eDiary.

Time frame: From baseline to week 12 and week 24

Population: Full Analysis Set (FAS) included all randomised participants who received at least one dose of study intervention. 'While on treatment' estimand strategy was followed, which means that if an intercurrent event occurs all subsequent data for that subject was excluded from the evaluation.

The mean change from baseline in Post-BD FEV1 at Week 12 was estimated using a repeated measures mixed effects analysis of covariance. Only subjects with non-missing covariates are included in the analysis. FEV1 was measured by spirometry at clinic.

Time frame: From baseline to week 12

Population: Full Analysis Set (FAS) included all randomised participants who received at least one dose of study intervention. 'While on treatment' estimand strategy was followed, which means that if an intercurrent event occurs all subsequent data for that subject was excluded from the evaluation.

Measurement of Maximum Plasma Concentration (Cmax) at pre-randomisation (baseline visit) and week 12.

Time frame: At week 12

Population: The PK set included all participants who had received mitiperstat and had evaluable PK data for mitiperstat, with no important protocol deviations that were thought to have impacted the analysis of the PK data.

Measurement of Time to Reach Maximum Plasma Concentration (Tmax) at pre-randomisation (baseline visit) and week 12.

Time frame: At week 12

Population: The PK set included all participants who had received mitiperstat and had evaluable PK data for mitiperstat, with no important protocol deviations that were thought to have impacted the analysis of the PK data.

A COPD exacerbation was considered moderate if it required treatment with systemic corticosteroids and/or antibiotics for at least 3 days or resulted in emergency room visit\< 24 hours requiring intensive treatment; and did not result in hospitalization or death. A COPD exacerbation was considered severe if it resulted in hospitalization (defined as an inpatient admission ≥ 24 hours in the hospital, an observation area, the emergency department, or other equivalent healthcare facility depending on the country and healthcare system) or death due to COPD.

Time frame: From baseline to up to week 24

Population: Full Analysis Set (FAS) included all randomised participants who received at least one dose of study intervention. 'While on treatment' estimand strategy was followed, which means that if an intercurrent event occurs all subsequent data for that subject was excluded from the evaluation.