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.

Status

Recruiting

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07785934

Enrollment

Registered

2026-08-25

Start date

2026-05-27

Completion date

2026-12-01

Last updated

2026-08-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Drug Drug Interaction (DDI), Pharmacokinetics and Pharmacodynamics

Keywords

UBT251 Injection, Drug-Drug Interactions, Pharmacokinetics, Pharmacodynamics, Obesity, Overweight

Brief summary

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.

Interventions

DRUGUBT251

Subcutaneous injection administered once weekly with dose escalation

DRUGMetformin hydrochloride

Oral administration. Metformin hydrochloride will be given as twice-daily doses for 7 consecutive administrations.

DRUGWarfarin Sodium

Oral administration. Warfarin sodium will be given as 2 single doses.

DRUGAtorvastatin calcium

Oral administration. Atorvastatin calcium will be given as 2 single doses.

DRUGDigoxin

Oral administration. Digoxin will be given as 2 single doses.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Area under plasma concentration-time curve of metformin (AUC0-τ) and S-warfarin, R-warfarin (AUC0-t, AUC0-∞)	From time 0 to 30 hours (metformin, post last dose) and 168 hours (S-warfarin, R-warfarin) after respective doses	Compare AUC0-τ of metformin after multiple-dose administration alone, and AUC0-t and AUC0-∞ of S-warfarin and R-warfarin after single-dose administration alone, with the corresponding parameters when these drugs are administered following dose-escalated and continued 6.0 mg UBT251 in Cohort 1.
Area under plasma concentration-time curve (AUC0-t and AUC0-∞) of atorvastatin and digoxin	From time 0 to 72 hours (atorvastatin) and 120 hours (digoxin) after respective single doses	Compare AUC0-t and AUC0-∞ of single-dose atorvastatin and single-dose digoxin administered alone, with corresponding parameters when administered following dose-escalated and continued 6.0 mg UBT251 in Cohort 2.

Secondary

Countries

China

Contacts

CONTACTWei Hu, PhD

hwgcp@ayefy.com+86-13856086475

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Aug 26, 2026

Measure	Time frame	Description
Terminal Rate Constant (λz) of R-warfarin in Cohort 1	Pre-dose and up to 168 hours following last dose at steady-state	Plasma concentrations of R-warfarin will be measured in samples collected pre-dose and up to 168 hours following the last dose at steady-state. This endpoint evaluates terminal rate constant (λz).
Terminal Half-Life (t1/2z) of R-warfarin in Cohort 1	Pre-dose and up to 168 hours following last dose at steady-state	Plasma concentrations of R-warfarin will be measured in samples collected pre-dose and up to 168 hours following the last dose at steady-state. This endpoint evaluates terminal half-life (t1/2z).
Apparent Clearance (CL/F) of R-warfarin in Cohort 1	Pre-dose and up to 168 hours following last dose at steady-state	Plasma concentrations of R-warfarin will be measured in samples collected pre-dose and up to 168 hours following the last dose at steady-state. This endpoint evaluates apparent clearance (CL/F).
Apparent Volume of Distribution (Vz/F) of R-warfarin in Cohort 1	Pre-dose and up to 168 hours following last dose at steady-state	Plasma concentrations of R-warfarin will be measured in samples collected pre-dose and up to 168 hours following the last dose at steady-state. This endpoint evaluates apparent volume of distribution (Vz/F).
Maximum Plasma Concentration (Cmax) of UBT251 in Cohort 1	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state maximum plasma concentration (Cmax).
Time to Maximum Plasma Concentration (Tmax) of UBT251 in Cohort 1	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state time to maximum plasma concentration (Tmax).
Area Under the Plasma Concentration-Time Curve From Zero to Last Measurable Time-point (AUC0-t) of UBT251 in Cohort 1	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state area under the concentration-time curve from zero to last measurable time-point (AUC0-t).
Terminal Rate Constant (λz) of UBT251 in Cohort 1	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state terminal rate constant (λz).
Terminal Half-Life (t1/2z) of UBT251 in Cohort 1	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state terminal half-life (t1/2z).
Apparent Clearance (CL/F) of UBT251 in Cohort 1	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state apparent clearance (CL/F).
Apparent Volume of Distribution (Vz/F) of UBT251 in Cohort 1	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state apparent volume of distribution (Vz/F).
Maximum Plasma Concentration (Cmax) of Atorvastatin in Cohort 2	Pre-dose and up to 72 hours following single dose	Plasma concentrations of atorvastatin will be measured in samples collected pre-dose and up to 72 hours following single dose. This endpoint evaluates maximum plasma concentration (Cmax).
Time to Maximum Plasma Concentration (Tmax) of Atorvastatin in Cohort 2	Pre-dose and up to 72 hours following single dose	Plasma concentrations of atorvastatin will be measured in samples collected pre-dose and up to 72 hours following single dose. This endpoint evaluates time to maximum plasma concentration (Tmax).
Terminal Rate Constant (λz) of Atorvastatin in Cohort 2	Pre-dose and up to 72 hours following single dose	Plasma concentrations of atorvastatin will be measured in samples collected pre-dose and up to 72 hours following single dose. This endpoint evaluates terminal rate constant (λz).
Terminal Half-Life (t1/2z) of Atorvastatin in Cohort 2	Pre-dose and up to 72 hours following single dose	Plasma concentrations of atorvastatin will be measured in samples collected pre-dose and up to 72 hours following single dose. This endpoint evaluates terminal half-life (t1/2z).
Apparent Clearance (CL/F) of Atorvastatin in Cohort 2	Pre-dose and up to 72 hours following single dose	Plasma concentrations of atorvastatin will be measured in samples collected pre-dose and up to 72 hours following single dose. This endpoint evaluates apparent clearance (CL/F).
Apparent Volume of Distribution (Vz/F) of Atorvastatin in Cohort 2	Pre-dose and up to 72 hours following single dose	Plasma concentrations of atorvastatin will be measured in samples collected pre-dose and up to 72 hours following single dose. This endpoint evaluates apparent volume of distribution (Vz/F).
Maximum Plasma Concentration (Cmax) of 2-hydroxy-atorvastatin in Cohort 2	Pre-dose and up to 72 hours following single dose	Plasma concentrations of 2-hydroxy-atorvastatin will be measured in samples collected pre-dose and up to 72 hours following single dose. This endpoint evaluates maximum plasma concentration (Cmax).
Time to Maximum Plasma Concentration (Tmax) of 2-hydroxy-atorvastatin in Cohort 2	Pre-dose and up to 72 hours following single dose	Plasma concentrations of 2-hydroxy-atorvastatin will be measured in samples collected pre-dose and up to 72 hours following single dose. This endpoint evaluates time to maximum plasma concentration (Tmax).
Terminal Half-Life (t1/2z) of UBT251 in Cohort 2	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state terminal half-life (t1/2z).
Apparent Clearance (CL/F) of UBT251 in Cohort 2	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state apparent clearance (CL/F).
Apparent Volume of Distribution (Vz/F) of UBT251 in Cohort 2	Pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing	Plasma concentrations of UBT251 will be measured in samples collected pre-dose and up to 672 hours following the final dose of UBT251 steady-state dosing. This endpoint evaluates steady-state apparent volume of distribution (Vz/F).
Area Under the INR-Time Curve (AUCINR) of Warfarin Under UBT251 Steady-State in Cohort 2	Baseline to 168 hours	Serial INR measurements are collected to characterize the pharmacodynamic effect of warfarin, when administered under UBT251 steady-state conditions. This endpoint evaluates area under the INR-time curve (AUCINR).
Maximum Observed INR (INRmax) of Warfarin Under UBT251 Steady-State in Cohort 2	Baseline to 168 hours	Serial INR measurements are collected to characterize the pharmacodynamic effect of warfarin administered under UBT251 steady-state conditions. This endpoint evaluates maximum observed INR (INRmax).
Change in Body Weight From Pre-treatment Baseline Following UBT251 Dosing in Cohort 2	throughout UBT251 titration period	Body weight is measured at baseline and scheduled visits. This endpoint evaluates body weight change relative to pre-UBT251 baseline.
Incidence, Maximum Severity Grade, and Duration of Adverse Events and Serious Adverse Events During UBT251 Treatment	Baseline up to Study Day 190	All adverse events and serious adverse events are actively monitored and recorded throughout the study. This outcome assesses the incidence defined as percentage of affected subjects, maximum severity grade classified according to CTCAE criteria, and duration in days of each adverse event.
Changes From Baseline in Vital Signs During UBT251 Treatment	Baseline up to Study Day 190	Vital signs including systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and body temperature are measured using standard clinical equipment at scheduled visits. This outcome evaluates absolute and relative changes from baseline throughout the study period.
Changes From Baseline in 12-Lead Electrocardiogram (ECG) Parameters During UBT251 Treatment	Baseline up to Study Day 190	12-lead ECGs are collected at scheduled visits and can be additionally performed at any time for safety monitoring. Participants rest in a supine position for at least 5 minutes before testing. Assessed parameters include RR interval, PR interval, heart rate, QRS interval, QT interval, QTc interval, and QTcF calculated by Fredericia's formula. This outcome evaluates parameter changes from baseline and clinically significant abnormal ECG findings.
Peak Plasma Concentration (Cmax) of metformin in Cohort 1	Up to 30 hours following last dose at steady-state	Peak plasma concentration (Cmax) of metformin at steady-state in Cohort 1
Time to Peak Plasma Concentration (Tmax) of metformin in Cohort 1	Up to 30 hours following last dose at steady-state	Time to reach peak plasma concentration (Tmax) of metformin at steady-state in Cohort 1
Area under the plasma concentration-time curve from 0 to last measurable time point (AUC0-t) of metformin in Cohort 1	Pre-dose and up to 30 hours following last dose at steady-state	Area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUC0-t) of metformin at steady-state in Cohort 1
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) of metformin in Cohort 1	Pre-dose and up to 30 hours following last dose at steady-state	Area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) of metformin at steady-state in Cohort 1
Apparent volume of distribution (Vz/F) of metformin in Cohort 1	Pre-dose and up to 30 hours following last dose at steady-state	Apparent volume of distribution (Vz/F) of metformin at steady-state in Cohort 1
Apparent total clearance (CL/F) of metformin in Cohort 1	Up to 30 hours following last dose at steady-state	Apparent total clearance (CL/F) of metformin at steady-state in Cohort 1
Terminal elimination rate constant (λz) of metformin in Cohort 1	Pre-dose and up to 30 hours following last dose at steady-state	Terminal elimination rate constant (λz) of metformin at steady-state in Cohort 1
Terminal half-life (t1/2z) of metformin in Cohort 1	Pre-dose and up to 30 hours following last dose at steady-state	Terminal elimination half-life (t1/2z) of metformin at steady-state in Cohort 1
Peak Plasma Concentration (Cmax) of S-warfarin in Cohort 1	Pre-dose and up to 168 hours following last dose at steady-state	Plasma concentrations of S-warfarin will be measured in samples collected pre-dose and up to 168 hours following the last dose at steady-state. This endpoint evaluates maximum plasma concentration (Cmax).
Time to Maximum Plasma Concentration (Tmax) of S-warfarin in Cohort 1	Pre-dose and up to 168 hours following last dose at steady-state	Plasma concentrations of S-warfarin will be measured in samples collected pre-dose and up to 168 hours following the last dose at steady-state. This endpoint evaluates time to maximum plasma concentration (Tmax).
Terminal Rate Constant (λz) of S-warfarin in Cohort 1	Pre-dose and up to 168 hours following last dose at steady-state	Plasma concentrations of S-warfarin will be measured in samples collected pre-dose and up to 168 hours following the last dose at steady-state. This endpoint evaluates terminal rate constant (λz).
Terminal Half-Life (t1/2z) of S-warfarin in Cohort 1	Pre-dose and up to 168 hours following last dose at steady-state	Plasma concentrations of S-warfarin will be measured in samples collected pre-dose and up to 168 hours following the last dose at steady-state. This endpoint evaluates terminal half-life (t1/2z).