Study to Assess the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of AZD0284 in Healthy Subjects

Exclusion Criteria

• •1. History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• •2. History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• •3. Any clinically significant illness, infection, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• •4. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the PI.
• •5. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV).
• •6. Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:
• •* Systolic BP (SBP) \< 90 mmHg or ≥ 140 mmHg
• •* Diastolic BP (DBP) \< 50 mmHg or ≥ 90 mmHg
• •* Pulse \< 45 or \> 85 beats per minute (bpm)
• •7. Any clinically significant abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12 Lead ECG as considered by the PI that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy. Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 450 ms or shortened QTcF \< 340 ms or family history of long QT syndrome.
• •8. PR(PQ) interval shortening \< 120 ms (PR \> 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular pre-excitation)
• •9. PR (PQ) interval prolongation (\> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree atrioventricular (AV) block, or AV dissociation.
• •10. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS \> 110 ms. Subjects with QRS \> 110 ms but \< 115 ms are acceptable if there is no evidence of e.g. ventricular hypertrophy or pre-excitation
• •11. Known or suspected history of drug abuse, as judged by the PI
• •12. Current smokers or those who have smoked or used nicotine products within the previous 3 months.
• •13. History of alcohol abuse or excessive intake of alcohol, as judged by the PI.
• •14. Positive screen for drugs of abuse or cotinine (nicotine) at screening or admission to the Unit or positive screen for alcohol on admission to the Unit prior to the first administration of IMP.
• •15. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD0284.
• •16. Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the PI.
• •17. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
• •18. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
• •19. Plasma donation within one month of screening or any blood donation/blood loss \> 500 mL during the 3 months prior to screening
• •20. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of investigational product 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.
• •21. Receipt of live viral or live bacterial vaccines (such as BCG) 3 months prior to randomization on Day 1.
• •22. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
• •23. Subjects who have previously received AZD0284
• •24. Involvement of any Astra Zeneca or study site employee or their close relatives.
• •25. Judgment by the PI 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.
• •26. Subjects who are vegans or have medical dietary restrictions.
• •27. Subjects who cannot communicate reliably with the PI.
• •28. Subject who have increased risk of infection
• •* History and/or presence of tuberculosis (TB); positive result for IFN-γ release assay (IGRA) (i.e. QuantiFERON TB-Gold) the test may be repeated if the initial test result is indeterminate. Subjects who have resided in regions where tuberculosis or mycosis are endemic during 90 days before screening or who intend to visit such a region during the duration of the study.
• •* Is in a high-risk group for HIV infection within the last 6 months.
• •* Subjects with active malignancy or neoplastic disease in the previous 5 years other than superficial basal cell carcinoma.
• •* Subjects who have received live or attenuated vaccine in the 4 weeks prior to dosing.
• •* Subjects with a disease history suggesting abnormal immune function.
• •In addition, the following is considered a criterion for the exclusion from the optional genetic component of the study:
• •29. Previous bone marrow transplant.
• •30. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.