Overweight,Obesity
Conditions
Brief summary
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.
Interventions
DRUGZT002 injection, metformin, warfarin
Drug: metformin Participants will receive metformin twice daily for 3.5 days in both periods Drug: warfarin Participants will receive a single dose of warfarin in both periods Drug: ZT002 Participants will receive multiple doses of ZT002 in the second period
DRUGZT002 injection, rosuvastatin, digoxin
Drug: rosuvastatin Participants will receive a single dose of rosuvastatin in both periods Drug: digoxin Participants will receive a single dose of digoxin in both periods Drug: ZT002 Participants will receive multiple doses of ZT002 in the second period
Sponsors
Beijing QL Biopharmaceutical Co.,Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the concentration-time curve of metformin within dosing interval (12 hours) at steady state | From Day 4 to Day 5, from Day 112 to Day 113 |
| Area under the concentration-time curve of S-warfarin from time zero to infinity after single-dose administration | From Day 6 to Day 13, from Day 126 to Day 133 |
| Area under the concentration-time curve of R-warfarin from time zero to infinity after single-dose administration | From Day 6 to Day 13, from Day 126 to Day 133 |
| Area under the concentration-time curve of rosuvastatin from time zero to infinity after single-dose administration | From Day 1 to Day 5, from Day 111 to Day 115 |
| Area under the concentration-time curve of digoxin from time zero to infinity after single-dose administration | From Day 5 to Day 12, from Day 125 to Day 132 |
Secondary
| Measure | Time frame |
|---|---|
| Maximal observed concentration of metformin at steady state | From Day 4 to Day 5, from Day 112 to Day 113 |
| Maximal observed concentration of S-warfarin after single-dose administration | From Day 6 to Day 13, from Day 126 to Day 133 |
| Maximal observed concentration of R-warfarin after single-dose administration | From Day 6 to Day 13, from Day 126 to Day 133 |
| Maximal observed concentration of rosuvastatin after single-dose administration | From Day 1 to Day 5, from Day 111 to Day 115 |
| Maximal observed concentration of digoxin after single-dose administration | From Day 5 to Day 12, from Day 125 to Day 132 |
| Area under the INR-time curve after single-dose warfarin administration | From Day 6 to Day 13, from Day 126 to Day 133 |
| Maximal INR after single-dose warfarin administration | From Day 6 to Day 13, from Day 126 to Day 133 |
| Percentage change in body weight | Day 13 and Day 133 in Cohort 1, Day 12 and Day 132 in Cohort 2 |
| Proportion of participants with positive anti-drug antibody against ZT002 | From Day 13 to Day 167 in Cohort 1, from Day 12 to Day 166 in Cohort 2 |
| Proportion of participants with treatment-emergent adverse events | From baseline to Day 167 in Cohort 1, from baseline to Day 166 in Cohort 2 |
| Proportion of participants with serious adverse events | From baseline to Day 167 in Cohort 1, from baseline to Day 166 in Cohort 2 |
Countries
China
Contacts
CONTACTPei Liu
PRINCIPAL_INVESTIGATORQin Yu, Master
West China Second University Hospital
Outcome results
None listed