Safety, tolerability and pharmacokinetics of multiple ascending doses of AZD8871 in healthy subjects

Inclusion Criteria

• Inclusion Criteria:
• 1) Provision of written informed consent prior to conducting any study-related procedures, including withdrawal of medications.
• 2) Male subjects aged 18 to 55 years, inclusive at Screening.
• 3) Body mass index (BMI) calculated as weight in kg/height in m2 from ≥18 to ≤30 kg/m2 and weight ≥50 kg at Screening.
• 4) Healthy, free from any clinically significant disease/ conditions (including all cardiovascular conditions), as determined by medical history, physical examination, clinical laboratory testing, 12-lead ECG findings at Screening and admission to the unit.
• 5) Spirometry readings (FEV1 and Forced Vital Capacity [FVC]) to be ≥80% of predicted value calculated using Quanjer 2012 reference equations (Quanjer et al 2012) at Screening.
• 6) Normal blood pressure (BP) (defined as systolic BP [SBP] ≥90 and ≤140 mmHg, and diastolic BP [DBP] ≥50 and ≤90 mmHg) at Screening and admission to the unit, measured after resting in supine position for at least 10 minutes.
• 7) Normal heart rate (HR) (defined as HR ≥45 and ≤90) measured after resting in supine position for at least 10 minutes at Screening and admission to the unit.
• 8) 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.
• 9) Negative for drugs of abuse and alcohol tests at Screening and admission to the unit.
• 10) Normal serum potassium at Screening and at admission to the unit.
• 11) Willing and able to comply with study specific procedures and restrictions
• Exclusion Criteria:
• 1) Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• 2) Surgical history clinically relevant for the purpose of the study or any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of Screening.
• 3) History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin.
• 4) Current smokers, or a smoking history during the last 6 months or total smoking history of more than 10 pack-years. Use of electronic cigarettes or other forms of nicotine, current use or use within the last 6 months.
• 5) Prolonged QTcF interval, >450 ms at Screening, or family history of long QT syndrome.
• 6) Any clinically significant arrhythmia noted on telemetry recording, prior to randomisation.
• 7) History of excessive use or abuse of alcohol within the past 2 years.
• 8) History of drug abuse within the past 2 years.
• 9) Donation or loss >400 ml of blood and plasma within the previous 3 months prior to Visit 1, Screening.
• 10) History of presence of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to any drug, as judged by the Investigator or history of hypersensitivity to drugs pharmacologically related to study drug.
• 11) PR (PQ) interval shortening <120 ms (PR >110 ms but <120 ms is acceptable if there is no evidence of ventricular pre-excitation) at Screening.
• 12) PR (PQ) interval prolongation (> 240 ms), intermittent second (Wenckebach block while asleep is not exclusive), or third degree atrioventricular block, or atrioventricular dissociation at Screening.
• 13) Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS >110 ms.
• 14) Subject who does not agree to follow instructions to avoid partner pregnancy.
• 15) Subject who is not able to adhere to the restrictions on prior and concomitant medications.
• 16) Used any investigational drug within 3 months prior to Screening or within the equivalent time of 5 half-lives of receiving the last administration, whichever is longer, or on an extended follow-up after receiving an IMP.
• 17) Subjects unable to communicate reliably with the Investigator.
• 18) Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.