Absolute Bioavailability and ADME Study of [14C]AZD9977 in Healthy Male Subjects

Inclusion Criteria: 1. Provision of signed and dated, written informed consent prior to any study specific procedures. 2. Healthy male subjects aged 30 to 60 years at the time of signing informed consent with suitable veins for cannulation or repeated venepuncture. 3. Body mass index (BMI) of 18.0 to 30.0 kg/m2 (body weight at least 50 kg), as measured at screening. 4. Must be willing and able to communicate and participate in the whole study. 5. Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day). 6. Must agree to adhere to the contraception requirements defined in the clinical protocol Exclusion Criteria: 1. History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study. 2. History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. Clinically significant history of recent depression, seizures or other hyperactive central nervous system condition or ongoing treatment for the same. 4. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977 or the formulation excipients. Hay fever is allowed unless it is active. 5. Acute diarrhoea or constipation in the 7 days before administration of IMP in the study. If screening occurs \>7 days before the first study day, this criterion will be determined on the first study day. 6. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP. 7. Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator. 8. Serum potassium \>5.0 mmol/L or fasting blood glucose \> upper limit of normal (ULN) at screening. 9. Evidence of renal impairment at screening, as indicated by an estimated eGFR of \<80 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or other evidence of renal impairment. 10. Subjects with known Gilbert's Syndrome or elevated unconjugated hyperbilirubinaemia or subjects with a history of cholecystectomy or gall stones. 11. Abnormal resting vital signs (after 5 min rest) of supine systolic BP \>140 mmHg and/or diastolic BP \>90 mmHg and/or \<50 mmHg and/or HR \<45 or \>90 bpm at screening or Period 1 Day 1 pre-dose. Vital signs can be repeated once if abnormal, as judged by the investigator. 12. Subjects with clinically significant history of recurrent syncope/blackouts or previous history of orthostatic hypotension or those who are noted to have a fall in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg or elevation in HR of more than 30 bpm when checked between 2 and 5 min after change of posture at screening or at Period 1 Day 1 pre-dose. 13. Any clinically significant abnormalities on 12-lead ECG, including those which can increase the risk of arrhythmias including QTcF\>450 msec, as judged by the investigator. 14. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), and human immunodeficiency virus (HIV) antibody. 15. Known or suspected history of drug abuse in the past 2 years, as judged by the investigator. 16. Has received another new chemical entity (defined as a compound which has not been approved for marketing; including radiolabelled chemical entity) within 90 days of Day 1 in this study. The period of exclusion lasts for 90 days after the final dose or 1 month after the last visit whichever is the longest. Note: subjects consented and screened, but not administered IMP in this study or a previous Phase I study, are not excluded. 17. Involvement of any AstraZeneca, Quotient Sciences or study site employee or their close relatives. 18. Subjects who report to have previously received AZD9977. 19. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening. 20. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 6 months prior to screening. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission. 21. Positive screen for drugs of abuse at screening or admission to the clinical unit or confirmed positive alcohol breath test at screening or admission to the clinical unit. 22. Known or suspected history of alcohol abuse or excessive intake of alcohol \>21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type). 23. Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate) as judged by the investigator. Excessive intake of caffeine defined as the regular consumption of more than 600 mg of caffeine per day (e.g., \>5 cups of coffee) or would likely be unable to refrain from the use of caffeine-containing beverages during confinement at the investigational site. 24. Use of any prescribed or non-prescribed medication including antacids, histamine receptor 2 (H2) antagonists, proton pump inhibitors and analgesics (other than up to 4 g paracetamol/acetaminophen per day), herbal remedies (including but not limited to, St. John's wort, kava, ephedra \[ma huang\], gingko biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto and ginseng), megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the two weeks prior to the first administration of IMP or longer if the medication has a long half-life. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the investigator. 25. Evidence of current SARS-CoV-2 infection. 26. Subjects with pregnant or lactating partners. 27. Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study. 28. Subjects who have been administered IMP in an 14C ADME study in the last 12 months. 29. Subjects who cannot communicate reliably with the investigator. 30. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order. 31. Judgment by the investigator that the volunteer 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. 32. Failure to satisfy the investigator of fitness to participate for any other reason.