Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of AZD8871 in Healthy Subjects

Number of Participants With ≥1 Treatment Emergent Adverse Event in Any Category.

Recording treatment emergent adverse events (TEAE). A TEAE was defined as an AE with onset (start date/time) after the first dose of investigational medicinal product. An AE 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 (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver) or the abnormal results of an investigation (e.g., laboratory findings, ECG).

Time frame: Change from baseline up to Days 25-27

Number of Participants With Clinically Relevant Abnormalities in Recording of Physical Examination.

A full physical examination included the examination of the following: general appearance, eyes, ears, nose, throat, chest/respiratory, heart/cardiovascular, gastrointestinal/liver, musculoskeletal/extremities, dermatological/skin, thyroid/neck, lymph nodes, neurological/psychiatric. A brief physical examination included assessment of the following: skin, lungs, cardiovascular system and abdomen (liver and spleen). A complete physical examination was performed at the Screening Visit. Any abnormal finding assessed as the investigator as clinically relevant was reported as an adverse event.

Time frame: Change from baseline up to Days 25-27

Number of Participants With Clinically Relevant Abnormalities in Vital Signs (Pulse, Blood Pressure and Body Temperature).

Systolic and diastolic BP (SBP/DBP) (in mmHg) measured after at least 10 minutes (could be reduced to 5 minutes at collection time points within the 1st hour after dosing) resting, and also before taking any blood sample and conducting any spirometry. Measurements were carried out with subject in the supine position and preferably always on the same arm. Subject's oral body temperature was measured at each vital signs collection.

Time frame: Change from baseline up to Days 25-27

Number of Participants With Clinically Relevant New Findings or Worsening of Pre-existing Findings as Assessed by Haematology.

Haematocrit, haemoglobin, erythrocytes (red blood cells), mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, leucocytes (white blood cells), differential blood count (neutrophils, lymphocytes, monocytes, eosinophils and basophils), and thrombocytes (platelets).

Time frame: Changes from baseline up to Days 25-27

Number of Participants With Clinically Relevant Abnormalities in 12-lead Safety ECG.

A 12-lead ECG was obtained after the subject rested in the supine position for at least 10 minutes (could be reduced to 5 minutes at collection time points within the first hour after dosing) (using the sites own ECG machines when not performing dECGs and using the same machine as the dECGs when time points coincided).

Time frame: Changes from baseline up to Days 25-27

Number of Participants With Clinically Relevant Abnormalities in Telemetry ECG.

Recording of telemetry findings. A 2-lead real-time telemetry ECG was performed for at least 4 hours on Day -1 and then on Days 1, 10 and 16 from 30 minutes pre-dose until 24 hours post-dose. The telemetry monitoring system was reviewed by the Investigator or research nurse and paper printouts of any clinically important events were stored as source data.

Time frame: Changes from baseline up to Day 20 (discharge from study unit)

Number of Participants With Clinically Relevant New Findings or Worsening of a Pre-existing Findings as Assessed by Clinical Chemistry.

Electrolytes: Sodium, potassium, calcium, chloride and inorganic phosphorus Enzymes: AST, ALT, ALP, GGT, LDH, creatine-kinase Substrates: Glucose (fasting), total cholesterol, triglycerides, creatinine, TBL, total protein, albumin, uric acid, urea and BUN Endocrinology: T4, TSH Viral Serology: HIV I and II antibodies, Hepatitis C antibodies, Hepatitis B surface antigen, Hepatitis B core (HBc) immunoglobulin antibodies Coagulation parameters: INR, PT, aPTT

Time frame: Changes from baseline up to Days 25-27

Number of Participants With Clinically Relevant New Findings or Worsening of Pre-existing Findings as Assessed by Urinalysis Report.

Dipstick analysis was performed at the centre and included: pH, blood, leucocytes, protein, glucose, bilirubin, urobilinogen, ketones and nitrites. If clinically relevant abnormalities were detected (positive result in dipstick), microscopy (RBC, WBC and casts \[Hyaline, Granular and Cellular\]) were performed.

Time frame: Changes from baseline up to Days 25-27

Number of Participants With Clinically Relevant Abnormalities in 12-lead dECG (Including High Precision QTc Analysis) Findings.

The AZ ECG Centre performed the digital ECG (dECG) analysis in this study, using the EClysis© system, version 3.3, or higher. At protocol-indicated time points, 12-lead continuous dECG was recorded over at least 5 minutes with the Schiller Cardiovit CS-200 recorder (Schiller AG, Baar, Switzerland) and transmitted to the AZ central dECG repository, according to AZ ECG Centre´s standard procedures for settings, recording and transmission of dECGs

Time frame: Changes from baseline up to Day 20