An Open-label Study in Healthy Participants to Evaluate AZD0780 as an Object or Precipitant of CYP3A4-mediated Drug-drug Interactions

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study-specificprocedures.

2. Healthy male and female participants of non-childbearing potential aged 18 to 75years with suitable veins for cannulation or repeated venipuncture. Part 4 only:Healthy female participants of non-childbearing potential aged 18 to 75 years withsuitable veins for cannulation or repeated venipuncture.

3. All females must have a negative pregnancy test at the Screening Visit and onadmission to the Clinical Unit.

4. Females of non-childbearing potential must be confirmed at the Screening Visit byfulfilling one of the following criteria:

5. Postmenopausal defined as amenorrhea for at least 12 months following cessationof all exogenous hormonal treatments and FSH levels in the postmenopausalrange.

6. Documentation of irreversible surgical sterilization by hysterectomy, bilateraloophorectomy, or bilateral salpingectomy but not tubal ligation or tubalocclusion.

7. Sexually active fertile male participants with partners of childbearing potentialmust adhere to the contraception methods detailed in Appendix C 2.1 from the time offirst administration of AZD0780 administration until 3 months after the studyFollow-up Visit.

8. Have a BMI between 18 and 35 kg/m2 inclusive and weight at least 50 kg at theScreening Visit and on admission to the Clinical Unit.

Exclusion Criteria:

1. History of any clinically important disease or disorder which, in the opinion of theInvestigator, may either put the participant at risk because of participation in thestudy, or influence the results or the participant's ability to participate in thestudy.

2. History or presence of gastrointestinal, hepatic, or renal disease or any othercondition known to interfere with absorption, distribution, metabolism, or excretionof drugs.

3. Any prior gastrointestinal surgery which may affect absorption, eg, gastric bypassor resection.

4. Any clinically important illness, medical/surgical procedure, or trauma within 4weeks of the first administration of study intervention.

5. Any laboratory values with the following deviations at the Screening Visit or onadmission to the Clinical Unit. Abnormal values may be repeated once at thediscretion of the Investigator.

6. Any clinically important abnormalities in clinical chemistry, hematology, orurinalysis results other than those described under exclusion criterion number 5, atscreening and/or admission to the Clinical Unit, as judged by the Investigator.Abnormal values may be repeated once at the discretion of the Investigator.

7. Any positive result at Screening for serum HBsAg, HBcAb, HCV, or HIV.

8. Any clinically significant abnormal findings in abnormal vital signs, after at least 10 minutes supine rest, at Screening and on admission to the Clinical Unit, asjudged by the Investigator. Abnormal values may be repeated once at the discretionof the Investigator..

9. Any clinically important abnormalities in rhythm, conduction or morphology of theresting ECG and any clinically important abnormalities in the 12-lead ECG asconsidered by the Investigator that may interfere with the interpretation of QTcinterval changes.

10. Current smokers or those who have smoked or used nicotine products (includinge-cigarettes) within the previous 3 months prior to screening.

11. Known or suspected history of alcohol or drug abuse or excessive intake of alcoholas judged by the Investigator.

12. Positive screen for drugs of abuse, alcohol, or cotinine at Screening or onadmission to the Clinical Unit.

13. History of severe allergy/hypersensitivity or ongoing clinically importantallergy/hypersensitivity, as judged by the Investigator or history ofhypersensitivity to drugs with a similar chemical structure or class to AZD0780,itraconazole (Part 1 only), carbamazepine (Part 2 only), midazolam (Part 3 only), orEE/LNG (Part 4 only).

14. Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate)defined as the regular consumption of more than 500 mg of caffeine per day (eg, > 5cups of coffee [one cup ~100 mg caffeine]; one cup of tea ~30 mg caffeine) or wouldlikely be unable to refrain from the use of caffeine-containing beverages duringconfinement at the Clinical Unit.

15. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeksprior to the first administration of study intervention.

16. Use of any prescribed or nonprescribed medication including hormone replacementtherapy, antacids or acid reducing agents (including proton pumpinhibitors),analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and mineralsduring the 2 weeks prior to the first administration of study intervention or longerif the medication has a long half-life.

17. Plasma donation within one month of the Screening Visit or any blood donation/bloodloss > 500 mL during the 3 months prior to the Screening Visit.

18. Has received another new chemical entity (defined as a compound which has not beenapproved for marketing) within 30 days or 5 half-lives (whichever is longest) of thefirst administration of the study intervention in this study. NOTE: participantsconsented and screened, but not enrolled/randomized in this study or a previousPhase I study, are not excluded. NOTE: All follow-up activities in a previousresearch study (including last study visit, unresolved AEs, or abnormal laboratoryvalues) have to be completed prior to the Screening Visit. NOTE: Participants mustbe checked in VCT in the USA.

19. Participants who have previously received AZD0780 within 60 days prior to Screening.

20. Current/previous use of drugs that reduce or inhibit PCSK9 (approved orinvestigational; within 12 months of enrolment). Any current/previous use ofinclisiran.

21. Elevated or abnormal liver enzymes or active liver disease, or who have experiencedliver toxicity with other drugs.

22. Known or confirmed for HLA-A3101 and/or HLA-B1502 allele at Screening (Part 2only).

23. Participant who previously experienced hypersensitivity reaction to anticonvulsantsincluding phenytoin, primidone, and phenobarbital.

24. Involvement in the planning and/or conduct of the study (applies to both AstraZenecastaff and/or staff at the Clinical Unit).

25. Judgment by the Investigator that the participant should not participate in thestudy if they have any ongoing or recent (ie, during the Screening period) minormedical complaints that may interfere with the interpretation of study data or areconsidered unlikely to comply with study procedures, restrictions, and requirements.

26. Participants who are vegans or have medical dietary restrictions.

27. Participants who cannot communicate reliably with the Investigator.

28. Vulnerable participants, eg, kept in detention, protected adults under guardianship,trusteeship, or committed to an institution by governmental or juridical order.