A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 After Single Ascending Doses to Healthy Males

Inclusion Criteria

• Provision of signed and dated written informed consent prior to any study specific procedures.
• Healthy male subjects aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture.
• Male subjects have to comply with the restrictions for sexual activity provided to them.
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Optional: Provision of signed and dated written informed consent for genetic research.

If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.

• Able to understand, read and speak the English language.

Exclusion Criteria

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influences the results or the potential subject's ability to participate in the study.
• History or presence of GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of dosing in Part A or the first dose of AZD9977 in Part B.
• Any clinically significant abnormalities in hematology, clinical chemistry or urinalysis results, as judged by the investigator.
• Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibodies.
• Abnormal findings in vital signs, after 10 minutes resting in the supine position, defined as any of the following:
• Systolic blood pressure (SBP) 90 bpm
• Any clinically important abnormalities in rhythm, conduction or morphology of the electrocardiogram (ECG) at screening or pre-dose, as considered by the investigator.
• Prolonged QTcF > 450 ms or family history of long QT syndrome.
• PR (PQ) interval shortening 110 ms but 240ms; intermittent second or third degree atrioventricular (AV) block, or AV dissociation.

Wenckebach block while asleep is not exclusive.

• Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 110 ms.

QRS > 110 ms but 500 mL during the 3 months prior to screening.

• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of dosing in Part A or the first dose of AZD9977 in Part B in this study. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest.

Note: Subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded.

• Involvement of any AstraZeneca or study site employee or their close relatives.
• Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
• Subjects who are vegans or have medical dietary restrictions (vegetarians may be included in the study).
• Subjects who cannot communicate reliably with the investigator.
• Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

In addition, any of the following is regarded as a criterion for exclusion from the genetic research:

• Previous bone marrow transplant.
• Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Criter