This is a randomized, placebo-controlled, double-blind study meaning neither the patient nor the study doctor will know which medication is being given. The study is randomized, meaning that participants will be randomly assigned to 1 of 3 treatment groups. To evaluate the efficacy, how the drug is absorbed in the blood stream and how safe is the study drug called AZD8871 when this is administered once daily during two weeks in patients with moderate to severe COPD.

Phase 1

Conditions: Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 19.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2016-002863-32-GB

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 42

Inclusion Criteria

1. Patient who provided of informed consent prior to any study-specific procedures
2. Male or female 40 to 80 years of age (both inclusive) at Screening (Visit 1). A female is eligible to enter and participate in the study if she is of non-childbearing potential.
3. Male patient should use a condom and spermicide to prevent pregnancy and drug exposure of a partner, regardless of the gender or childbearing potential of the partner first administration of the IP until 3 months after the last administration of the IP.
4. COPD Diagnosis: Patient with an established clinical history of COPD for more than 1 year at Screening, according to the GOLD 2016 COPD guidelines.
5. Tobacco Use: Patient is a current or former smoker with a history of =10 pack-years of cigarette smoking. A former smoker is defined as one who has stopped smoking for at least 6 months prior to Screening.
6. Patient with post-bronchodilator FEV1/FVC ratio <70% based on the value reached after inhalation of salbutamol (400 µg) at Visit 2. If criterion is not met, the test can be repeated at the latest, up to Day 14.
7. Patient with post-bronchodilator FEV1 that must be =40% and <80% predicted normal value at Visit 2. If criterion is not met, the test can be repeated at the latest, up to Day 14.
8. Patient who fulfils reversibility criteria to salbutamol at Visit 2. Reversibility is defined as =12% and =200 mL increase in FEV1 after inhalation of 4 puffs of salbutamol (400 µg). If the criterion is not met, the test can be repeated at the latest, up to Day 14.
9. Patient is willing and, in the opinion of the Investigator, able to change current COPD therapy as required by the protocol and willing to use ipratropium QID (if needed, during run-in and wash-out periods) with or without ICS for maintenance therapy of COPD and rescue medication salbutamol (as needed ) from Visit 1 up Visit 11.
10. Patient is free from any clinically active disease other than COPD that may impact study outcome, as determined by medical history, physical examination, laboratory testing, and 12-lead ECG findings, at Screening.
11. Patient is willing to remain at the study centre as required per-protocol to complete all visit assessments.
12. Patient with body mass index (BMI) <40 kg/m2 at the time of screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion Criteria

1. Patient previously enrolled in the present study.
2. Patient has significant diseases other than COPD, ie, disease or condition or an abnormality in laboratory, ECG, medical history or physical examination which, in the opinion of the Investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patient's ability to participate in the study.
3. Childbearing potential female, pregnant or lactating.
4. Patient who, in the opinion of the Investigator, has a current diagnosis of asthma.
5. Patient has alpha-1 antitrypsin deficiency as the cause of COPD.
6. Patient has other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or uncontrolled sleep apnoea. Allergic rhinitis is not exclusionary.
7. Lung surgery for volume reduction or lung transplantation: Patient has undergone lung volume reduction surgery, lobectomy, or bronchoscopic lung volume reduction (endobronchial blockers, airway bypass, endobronchial valves, thermal vapour ablation, biological sealants, massive pulmonary embolism and airway implants) within 1 year of Screening (Visit 1).
8. Patient is using nocturnal positive pressure (eg, continuous positive airway pressure or bi level positive airway pressure). Patient is using any non-invasive positive pressure ventilation device.
Note: A patient using continuous positive airway pressure or bi level positive airway pressure for Sleep Apnoea Syndrome is allowed in the study.
9. Patient who had 2 or more exacerbations of COPD (moderate or severe in intensity) within the last year prior to Screening (see Section 3.9 for definition of exacerbation of COPD)
10. Patient has been hospitalised due to poorly controlled COPD within 3 months of Screening.
11. Patient has acute worsening of COPD that requires treatment with corticosteroids or antibiotics in the 6 week interval prior to Screening (Visit 1), or during the Screening Period (between Visits 1 and 3).
12. Patient has had lower respiratory tract infections that required antibiotics within 6 weeks prior to Screening.
13. Patient cannot perform acceptable spirometry, ie, meet American Thoracic Society (ATS)/European Respiratory Society (ERS) acceptability criteria.
14. Patient has changed their smoking status (ie, start or stop smoking) or initiation of a smoking cessation program within 6 weeks of Screening.
15. Patient has participated in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening or who will enter the acute phase of a pulmonary rehabilitation program during the study. A patient in the maintenance phase of a pulmonary rehabilitation program is not to be excluded.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of inhaled AZD8871 in patients with moderate to severe COPD patients.;Secondary Objective: To investigate the pharmacokinetics of AZD8871 and its metabolites after multiple dose administration of AZD8871 in patients with moderate to severe COPD.;Primary end point(s): Change from baseline in Trough FEV1 on Day 15.;Timepoint(s) of evaluation of this end point: Day 15

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Day 1, Day 14;<br> Secondary end point(s): On serial PK sampling days, the following PK parameters will be calculated for AZD8871 and its metabolites LAS191861 and LAS34850 when applicable.<br> Day 1: Cmax, tmax, AUClast, AUC(0-24)<br> Day 14: Cmax, tmax, AUClast, AUC(0-24), Cavg, %Fluctuation, Rac(Cmax) and Rac(AUC(0-24))<br>

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