Phase I Drug-Drug Interaction Study of UBT251 Injection in Participants With Overweight or Obesity

A Phase 1, Open-Label, Drug-Drug Interaction Study to Evaluate the Effect of UBT251 on the Pharmacokinetics of Single Oral Doses of Metformin, Warfarin, Atorvastatin, and Digoxin in Overweight or Obese Participants.

This is a Phase I, open-label, two-cohort study designed to evaluate the drug-drug interaction potential of multiple-dose UBT251 Injection in adult participants with overweight or obesity.

The primary objective of Cohort 1 is to evaluate the effect of UBT251 Injection on the pharmacokinetic (PK) profiles of metformin and warfarin. The secondary objectives of Cohort 1 are to assess the influence of UBT251 Injection on the pharmacodynamic (PD) characteristics of warfarin, to evaluate the safety of UBT251 Injection administered alone, as well as metformin and warfarin administered alone or in combination with UBT251 Injection, and to characterize the PK, PD, and immunogenicity profiles following repeated UBT251 Injection dosing.

The primary objective of Cohort 2 is to evaluate the effect of UBT251 Injection on the PK profiles of atorvastatin and digoxin. The secondary objectives of Cohort 2 are to evaluate the safety of UBT251 Injection alone, atorvastatin and digoxin alone, and their combination with UBT251 Injection, as well as to assess the PK, PD, and immunogenicity characteristics after multiple administrations of UBT251 Injection.

Inclusion Criteria:

1. Participants with overweight or obesity, aged 18-45 years inclusive; Cohort 1 includes male participants only, and Cohort 2 includes both male and female participants.
2. Body weight ≥50.0 kg, body mass index (BMI) ranging from 24.0 to 35.0 kg/m² inclusive (BMI = weight(kg)/height²(m²)).
3. Participants (including their partners) have no plan to conceive from screening through 6 months after study completion, are willing to adopt contraceptive measures specified in the study, and have no plan to donate sperm or ova within 6 months after trial completion.
4. Participants are able to communicate well with investigators, have fully understood this study, voluntarily participate in it, understand and comply with all study requirements, and provide written informed consent.

Exclusion Criteria:

1. Known hypersensitivity or intolerance to investigational product or its excipients, or hypersensitivity to other GLP-1, GIP, GCG receptor agonists; or prior history of multiple or severe clinically significant drug hypersensitivity reactions; or active allergic disease or high-sensitivity constitution;

2. History or evidence of any of the following diseases:

   1. Personal or family history (first-degree relatives: parents, children or siblings) of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2);
   2. History of malignancy within 5 years prior to screening, except for adequately treated carcinoma in situ of the cervix, basal-cell or squamous-cell skin cancer, radically resected local prostate cancer, and radically resected ductal carcinoma in situ of the breast;
   3. History of acute or chronic pancreatitis, pancreatic injury, or pancreatic surgery;
   4. History of acute cholecystitis, cholelithiasis or severe gallbladder polyps within 6 months prior to screening, for which the investigator assesses that study participation may increase the participant's risk;
   5. History of dysphagia or any gastrointestinal disorder affecting drug absorption;
   6. Cardiovascular, respiratory, hepatic, gastrointestinal (including disorders markedly affecting gastric emptying or gastric motility, e.g. severe gastric spasm or pyloric stenosis), endocrine (including but not limited to history of thyroid carcinoma or preneoplastic lesions), hematological, neurological diseases, or muscular degenerative disorders that may significantly affect drug absorption, metabolism or elimination, increase participant risk, or confound data interpretation;
   7. History of severe hypoglycemic coma; or ≥3 episodes of blood glucose <3.9 mmol/L within any one week in the 2 months before screening (regardless of symptoms); or ≥1 episode of severe hypoglycemia per month within 2 months before screening (blood glucose <3.0 mmol/L accompanied by cognitive impairment or requiring third-party assistance);
   8. History of severe psychiatric disorders (including but not limited to suicidal ideation or suicide attempt, schizophrenia, bipolar disorder); or Patient Health Questionnaire-9 (PHQ-9) score ≥10 at screening;

3. Severe infection, trauma or major surgical operation within 4 weeks prior to screening; or planned surgical procedure during the study;

4. History of bariatric surgery for obesity;

5. Use of dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1, GCG, GIP or amylin-targeted agents (e.g. exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide, mazdutide, etc.) within 2 months before drug administration; or prior intolerance to the above-mentioned agents;

6. Use of any medicinal products within 14 days or 5 half-lives (whichever is longer) prior to drug administration; and planned use of any medicinal products (prescription, over-the-counter, herbal medicines) and/or dietary supplements during the study;

7. Abnormal findings with clinical significance as judged by the investigator in physical examination, vital signs, 12-lead electrocardiogram, or abdominal ultrasound at screening (mild-to-moderate fatty liver is excluded);

8. Any clinically significant laboratory abnormality meeting any of the following criteria at screening:

   1. Hepatic impairment: serum ALT or AST >1.5 × upper limit of normal (ULN), or total serum bilirubin >1 × ULN;
   2. Estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m²;
   3. Fasting blood glucose ≥7 mmol/L or <3.9 mmol/L; or HbA1c ≥6.5%;
   4. Fasting triglycerides ≥4.5 mmol/L;
   5. Hemoglobin <110 g/L for male participants, <100 g/L for female participants;
   6. International normalized ratio (INR) >1.3;
   7. Serum calcitonin ≥20 pg/mL (i.e. 20 ng/L);
   8. Clinically significant abnormalities in thyroid function tests at screening;
   9. Positive hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or syphilis antibody at screening, or findings judged clinically meaningful by the investigator;
   10. Any laboratory abnormality of clinical significance that, in the investigator's opinion, may interfere with evaluation of study results;

9. Blood loss or blood donation exceeding 400 mL, or receipt of blood or blood-component transfusion within 3 months before drug administration; or planned blood donation during the study;

10. Vaccination within 1 month prior to screening, or planned vaccination during the study;

11. Alcohol and tobacco overuse: average alcohol intake ≥14 standard units per week within 6 months before screening (1 unit = 285 mL beer, or 25 mL spirits, or 100 mL wine); average daily cigarette consumption ≥5 cigarettes, and inability to abstain during the study; positive blood alcohol test or result >0 mg/100 mL;

12. Consumption of special diets (including grapefruit, pomelo, etc.) or strenuous exercise within 14 days before drug administration; or intake of chocolate, any caffeine- or xanthine-containing food or beverages within 48 hours before drug administration; or other factors at screening that may affect drug absorption, distribution, metabolism or excretion;

13. History of drug abuse or illicit-drug use within 1 year prior to drug administration; or positive urine drug screen;

14. Female participants who are pregnant or lactating;

15. Intolerance to venipuncture; or history of vasovagal reaction to injection or blood;

16. Inability to maintain consistent diet and physical activity during the study; or special dietary requirements preventing compliance with standardized study diet;

17. Participation in another clinical trial within 3 months prior to drug administration (excluding screening-only participation without study drug administration or non-interventional studies);

18. Other conditions that, in the investigator's opinion, may affect PK assessment, may prevent the participant from completing the study, may expose the participant to substantial risk from study participation, or otherwise render the participant unsuitable or unable to participate in this study.