A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD0780 in Healthy Subjects

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study specificprocedures (including the Pre Screening Visit for Part B).

• Healthy male and female subjects (of nonchildbearing potential), aged 18 to 55 yearsinclusive, with suitable veins for cannulation or repeated venipuncture.

• Females must have a negative pregnancy test at the Screening Visit and on admissionto the study center, must not be lactating and must be of non childbearingpotential, confirmed at the Screening Visit by fulfilling one of the followingcriteria:

1. Postmenopausal defined as amenorrhea for at least 12 months or more followingcessation of all exogenous hormonal treatments and FSH levels in thepostmenopausal range.

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

• Have a BMI between 18 and 35 kg/m2 inclusive and weigh at least 50 kg and no morethan 120 kg inclusive at the Screening Visit and on admission to the study center.

• For Japanese subjects (Part B) and Chinese subjects (Part A):

1. A subject will be considered Japanese if both parents and all grandparents areJapanese, the subject was born in Japan, and the subject has not lived outsideJapan for more than 10 years.

2. A subject will be considered Chinese if both parents and all grandparents areChinese, the subject was born in China, and the subject has not lived outsideChina for more than 10 years.

• For Part B (MAD), at the Screening Visit subjects must have LDL-C ≥ 70 mg/dL but ≤ 190 mg/dL (or ≥ 1.8 mmol/L but ≤ 4.9 mmol/L for London EPCU [Early Phase ClinicalUnit]), and triglycerides < 400 mg/dL (or < 10.3 mmol/L for London EPCU).

• For Part B (rosuvastatin global MAD), at the Screening Visit subjects must haveLDL-C ≥ 100 mg/dL but < 190 mg/dL (≥ 2.6 mmol/L but ≤ 4.9 mmol/L for London EPCU).

Exclusion Criteria:

• History of any clinically important disease or disorder.

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

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

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first vaccinationwithin 30 days prior to randomization.

• SARS-CoV-2 second vaccination within 10 days of screening.

• Confirmed Coronavirus disease 2019 (COVID-19) infection during screening andadmission, by Polymerase Chain Reaction (PCR) test (in the London EPCU, COVID-19infection before or during Screening and/or admission will be confirmed by aCOVID-19 test. Subjects will undergo COVID-19 testing prior to ICF signing and anysubject testing positive will not be screened for the study).

• Any clinically important abnormalities in clinical chemistry, coagulation,hematology, or urinalysis results.

• Any positive result on Screening for serum hepatitis B surface antigen, hepatitis Cantibody, and Human immunodeficiency virus (HIV).

• Abnormal vital signs after 10 minutes supine rest at the Screening Visit and onadmission to the study center.

• Any clinically important abnormalities in rhythm, conduction or morphology of theresting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG that may interfere with the interpretation of ECG interval measured fromthe onset of the QRS complex to the end of the T wave (QT) corrected for heart rate (QTc) interval changes including abnormal ST-T-wave morphology at the ScreeningVisit and/or on admission to the study center.

• Known or suspected history of drug abuse.

• Current smokers or those who have smoked or used nicotine products within theprevious 3 months.

• History of alcohol abuse or excessive intake of alcohol.

• Positive screen for drugs of abuse, cotinine (nicotine), or alcohol at Screeningand/or admission to the study center.

• History of severe allergy/hypersensitivity or ongoing clinically importantallergy/hypersensitivity, or history of hypersensitivity to drugs with a similarchemical structure or class to AZD0780.

• Excessive intake of caffeine-containing drinks or food.

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

• Use of any prescribed or nonprescribed medication including antacids, analgesics,herbal remedies, mega-dose vitamins, and minerals during the 2 weeks prior to thefirst administration of IMP or longer if the medication has a long half-life.

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

• Has received another new chemical entity within 30 days or 5 half-lives of the firstadministration of IMP in this study.

• Subjects who have previously received AZD0780 within 60 days of the firstadministration of IMP in this study.

• Involvement of any Astra Zeneca or study center employee or their close relatives.

• Any ongoing or recent minor medical complaints that may interfere with theinterpretation of study data or are considered unlikely to comply with studyprocedures, restrictions, and requirements.

• Subjects who are vegans or have medical dietary restrictions.

• Subjects who cannot communicate reliably with the investigator.

• Vulnerable subjects.