Two-part Safety, Tolerability, Pharmacodynamic and -Kinetic Study of Inhaled AZD8871 in Asthmatic and COPD Subjects

Inclusion Criteria:Part 1

• Subjects who are able and willing to provide written informed consent prior to conducting any study-related procedures, including withdrawal of medications
• Adult male subjects aged 18 to 70 years (both inclusive)
• Body mass index (BMI) from 18 to 32 kg/m2 at screening
• Clinical diagnosis of asthma (according to the Global Initiative for Asthma [GINA] guidelines) for at least 6 months prior to screening
• Ability to change current asthma therapy, to discontinue previous prescribed medications after signature of informed consent as per required washout periods
• Screening FEV1 value of ≥70% of the predicted normal value
• FEV1 reversibility of ≥12% and an absolute increase of at least 200 mL over the baseline value within 30 min after inhalation of 400 µg (4 puffs) of salbutamol via a metered dose inhaler, with spacer device
• Subjects using intermittent salbutamol and / or subjects on a stable dose of low dose Inhaled corticosteroid (as defined by the GINA guidelines) at least 4 weeks prior to screening
• Predose FEV1 value of first treatment period within the range of ± 20% of the FEV1 measured at screening prior to salbutamol inhalation
• No current smokers, no subjects with a smoking history during the last 12 months and no subjects with a total smoking history of more than 10 pack-years
• No other relevant pulmonary disease or history of thoracic surgery
• Subjects who are otherwise healthy as determined by medical history, physical examination, 12-lead ECG findings
• Normal blood pressure (defined as Systolic blood pressure [SBP] between 100 and 140 mmHg for subjects ≤59 years of age and between 100 and 150 mmHg for subjects ≥60 years of age, and Diastolic blood pressure [DBP] between 40 and 90 mmHg) at screening
• Subjects whose clinical laboratory test results are not clinically relevant and are acceptable to the Investigator.
• Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibody (IgM), hepatitis C antibody and human immunodeficiency virus (HIV) I and II antibodies at screening
• Subjects who are negative for drugs of abuse and alcohol tests at screening and admission
• Subjects able to perform repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005(9) criteria at screening

Inclusion Criteria: Part 2

• Adult male and non-childbearing female subjects aged ≥40 years with a clinical diagnosis of stable moderate to severe COPD according to GOLD guidelines at screening
• Females must be of non-childbearing potential, confirmed at screening by fulfilling study predefined criteria
• Post-salbutamol FEV1 10 h per day (for Part 2 only)
• Use of systemic steroids for respiratory reasons within 6 weeks prior to screening
• Lower respiratory tract infection within 6 weeks prior to screening or prior to randomisation
• Upper respiratory tract infection requiring antibiotics within 6 weeks prior to screening or prior to randomisation
• Current history of tuberculosis, bronchiectasis or other non-specific pulmonary disease
• Subject with significant cardiovascular disease that may be vulnerable to cardiovascular instability
• QTcF (QT interval corrected, Fridericia formula QT[msec]/RR[s]) interval, >450 ms for males and >470 ms for females at screening or prior to randomisation, or history of long QT syndrome
• PR (duration in milliseconds from the beginning of wave P to onset of ventricular depolarisation [Q or R]) interval >200 ms at screening or prior to randomisation (for Part 1 only) Note: 4- 6 hours of ECG rhythm monitoring with telemetry will be performed on Day-1 to identify patients that may have any clinical significant abnormality prior to randomisation. If this occurs, patients should not participate in the study
• Subjects with serum potassium concentration 400 ml of blood and plasma within the previous 3 months prior