ZT002 is an ultralong-acting glucagon-like peptide-1. This open-label, fixed sequence, two-period crossover drug-drug interaction study is designed to evaluate the impact of ZT002 on the PK of metformin, warfarin, rosuvastatin and digoxin. The study will include obese and overweight but otherwise healthy participants aged 18 - 45.

The study consists of two cohorts. Each participant can only join one of the cohorts.

Cohort 1 evaluates the impact of ZT002 on the PK of metformin at steady state and on the PK of a single dose of warfarin. Participants are screened within 2 weeks before study drug administration. In the first period, metformin is given twice daily for 3.5 days and warfarin is given as a single dose without ZT002. In the second period, metformin and warfarin are given, following the same dose and regimen as in the first period, concomitantly with ZT002, which reaches steady state by up-titration. The participants will be followed up for 6 weeks after the last dose of ZT002.

Cohort 2 evaluates the impact of ZT002 on the PK of single doses of rosuvastatin and digoxin. Participants are screened within 2 weeks before study drug administration. In the first period, rosuvastatin and digoxin are given as single doses without ZT002. In the second period, rosuvastatin and digoxin are given, following the same dose and regimen as in the first period, concomitantly with ZT002, which reaches steady state by up-titration. The participants will be followed up for 6 weeks after the last dose of ZT002.

Inclusion Criteria:

• Age between 18 - 45 years (both inclusive) at the time of signing of the informed consent;
• Male (body weight >60.0 kg) or female (body weight >55.0 kg). Body mass index (BMI) 24.0 - 35.0 kg/m²(both inclusive);
• Considered to be generally healthy based on physical examination, and the results of vital signs, 12-lead electrocardiogram and clinical laboratory tests (hematology, urinalysis, chemistry, coagulation), as judged by the investigator.

Exclusion Criteria:

• Clinically significant diseases detected within 6 months before screening (including but not limited to neurological, psychiatric, cardiovascular, endocrine, gastrointestinal, respiratory, urinary, hematological, immunological diseases), judged by the investigator as possible to influence the study result or introduce safety risk to study drug administration;
• History of dysphagia or any gastrointestinal tract disease that affects drug absorption;
• Known hypersensitivity (asthma, hypersensitivity to GLP-1 receptor agonists or excipients), or known hypersensitivity to ZT002 injection;
• History of inspirational pneumonia within 5 years before screening;
• Medical history of hypoglycemia within 6 months before screening;
• History of acute or chronic pancreatitis;
• Cholelithiasis ≤ 1 cm, or history of cholecystitis or other symptomatic gallbladder disease, with the exception of cholecystectomy > 6 months prior to screening;
• History or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2;
• Glycated hemoglobin (HbA1c) ≥ 6.5% or fasting plasma glucose ≥ 7.0 mmol/L at screening;
• Aspartate aminotransferase ≥ 2 × upper limit of normal (ULN), Alanine aminotransferase ≥ 2 × ULN,
• Alkaline phosphatase total bilirubin ≥ 1.5 × ULN;
• Calcitonin above ULN at screening;
• Thyroid stimulating hormone (TSH) < 0.4 or >6.0 mIU/L;
• Use of hypoglycemic drugs (e.g. insulin, insulin secretagogues, thiazolidinedione, sodium-dependent glucose transporters 2 inhibitors [SGLT2i], dipeptidyl peptidase 4 inhibitor [DPP-4i], glucagon-like peptide-1 receptor agonist [GLP-1RA], metformin, α-glucosidase inhibitor) within 3 months before screening;
• Use of prescription drugs, over-the-counter drugs, dietary supplements, vitamins, or herbal medicines (excluding topical eye/nose drops and external use on the skin without systemic exposure risk) within 2 weeks before screening.

Exclusion criteria only applicable to Cohort 1:

• History that increases risk of bleeding, e.g. aneurysm, aortic dissection, cerebral vascular malformation, acute gastritis, gastric or duodenal ulcer; hemorrhoid bleeding within 1 month prior to screening;
• Hypersensitivity to metformin or warfarin;
• Prothrombin time (PT), international normalized ratio (INR) or activated partial thromboplastin time (APTT) above ULN and judged as clinically significant by investigator;
• Platelet < 100x109/L;
• Ventricular rate < 50 or > 100 bpm, second or third degree of atrioventricular block, left bundle branch block, complete right bundle branch block, or QT interval corrected by Fridericia's formula (QTcF) > 450 ms, or other abnormal electrocardiogram of clinical significance.

Exclusion criteria only applicable to Cohort 2:

• History of unexplained myalgia or myasthenia, or diagnosed with rhabdomyolysis;
• Hypersensitivity to rosuvastatin or digoxin;
• Unexplained creatine kinase above ULN;
• Serum potassium out of reference range;
• Ventricular rate < 55 or > 100 bpm, atrial fibrillation, atrioventricular block of any degree, preexcitation syndrome, left bundle branch block, complete right bundle branch block, or QT interval corrected by Fridericia's formula (QTcF) > 450 ms, or other abnormal electrocardiogram of clinical significance.