A 2-part, Randomised, Placebo-controlled, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of AZD8871 Delivered by Inhalation in Asthmatic and Chronic Obstructive Pulmonary Disease (COPD) Subjects

Number of Participants With Clinically Relevant Abnormalities in Blood Pressure

Time Frame: From the time of informed consent up to 36 hours after last dose of IP.

Blood pressure (BP) measurements (diastolic \[DBP\] and systolic BP \[SBP\]) taken after \~5 minutes rest in supine position, at screening, baseline (≤1 hour before IP administration), 10 and 30 minutes, 1, 2, 3, 4, 8, 12 hours (Day 1) and 24 and 36 hours (Day 2) after IP administration. Normal BP at screening: SBP 100-140 mmHg (subjects aged ≤59 years) and 100-150 mmHg (subjects aged ≥60 years), and DBP 40-90 mmHg. Criteria for notable changes in BP: High SBP: (≥180 and increase over baseline (predose) ≥20) or (≥200 and baseline \<200) Low SBP: (≤ 90 and decrease over baseline ≥20) or (≤75 and baseline \>75) High DBP: (≥105 and increase over baseline ≥15) or (≥115 and baseline \<115) Low DBP: (≤50 and decrease over baseline ≥15) or (≤40 and baseline \>40) All out of range values were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until considered non-clinically relevant.

The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event

Time Frame: From the time of informed consent up to 14 (±2) days after the last dose of investigational product. Unresolved AEs were followed up by the investigator for as long as medically indicated.

An adverse event is the development of an undesirable medical condition, or the deterioration of a pre-existing medical condition, following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms, signs, or the abnormal results of laboratory parameters (haematology, blood chemistry, urinalysis, physical examination, 12-lead ECGs and telemetry, and vital signs). AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 18.1.

Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters).

Time Frame: From the time of informed consent up to 36 hours after last dose of IP.

HR, QTcF and other ECG abnormalities were assessed by local digital 12-lead ECG performed in triplicate at the time points indicated: ECG (Parts 1 and 2) was assessed at Screening, Day 1 baseline, 10 min, 30 min, 1 hour (h), 2 h, 3 h, 4 h, 8 h, 12 h, 24 h, 36 h after dosing. Telemetry (Part 1), assessed with at least 2 lead real time display, was recorded at Day -1 (4-6 hours continuous recording, at the time this was more convenient for the logistics of the unit) and on Day 1 from the time of the IP administration up to at least 24 hours, but if advised by the Investigator or designee, then up to 36 hours after IP administration. Abnormal findings were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until the abnormality was considered non-clinically relevant.

Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis

Time Frame: From the time of informed consent up to 7 days after the last dose of IP.

A composite of clinically relevant abnormalities in clinical biochemistry, hematology and urinalysis laboratory evaluations. Laboratory tests (haematology, blood chemistry, and urinalysis) were performed at screening, at Day -1 (Part 1 only), at 24 hours (Day 2) and at follow-up (7 \[±2\] days) after IP administration. Coagulation was only performed at screening; TSH, T4 only at screening, at Day-1 and at follow-up. Abnormal findings were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until the abnormality was considered non-clinically relevant.

Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2

Time Frame: Baseline (Day 1) to 36 hours post-dose (Day 2)

Pharmacodynamics of AZD8871 before (-45 min and -15 min pre-dose) and after single dosing of AZD8871 Forced expiratory volume in 1 second (FEV1) on Day 2 (defined as the average of the values 23:00 and 24:00 hours after the morning dose of investigational product)