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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
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
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
West China Second Hospital, Sichuan University
Chengdu, Sichuan, China
RECRUITINGArea under the concentration-time curve of metformin within dosing interval (12 hours) at steady state
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From Day 5 to Day 12, from Day 125 to Day 132
Maximal observed concentration of metformin at steady state
Time frame: From Day 4 to Day 5, from Day 112 to Day 113
Maximal observed concentration of S-warfarin after single-dose administration
Time frame: From Day 6 to Day 13, from Day 126 to Day 133
Maximal observed concentration of R-warfarin after single-dose administration
Time frame: From Day 6 to Day 13, from Day 126 to Day 133
Maximal observed concentration of rosuvastatin after single-dose administration
Time frame: From Day 1 to Day 5, from Day 111 to Day 115
Maximal observed concentration of digoxin after single-dose administration
Time frame: From Day 5 to Day 12, from Day 125 to Day 132
Area under the INR-time curve after single-dose warfarin administration
Time frame: From Day 6 to Day 13, from Day 126 to Day 133
Maximal INR after single-dose warfarin administration
Time frame: From Day 6 to Day 13, from Day 126 to Day 133
Percentage change in body weight
Time frame: 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
Time frame: 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
Time frame: From baseline to Day 167 in Cohort 1, from baseline to Day 166 in Cohort 2
Proportion of participants with serious adverse events
Time frame: From baseline to Day 167 in Cohort 1, from baseline to Day 166 in Cohort 2
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