DR10624 is an Fc fusion protein tri-agonist with balanced glucagon-like peptide-1 receptor (GLP-1R)/glucagon receptor (GCGR)/ fibroblast growth factor 21 receptor (FGF21R) agonizing activities. The objectives of the planned clinical investigation will be to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single- and multiple-ascending doses of DR10624 via subcutaneous (SubQ) injection in a randomized, placebo-controlled, double-blind study.
This study includes 2 parts( 1 and 2). Part 1 involves a single dose of DR10624 taken as a subcutaneous injection just under the skin. Part 2 involve multiple doses of DR10624 taken as a subcutaneous injection (SC) just under the skin. Each participant will enroll in only one part.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
153
administered via subcutaneous injection
administered via subcutaneous injection
New Zealand Clinical Research
Christchurch, Canterbury, New Zealand
Number of participants with one or more treatment-emergent adverse event (TEAE), serious adverse event (SAE) and adverse event of special interest (AESI).
Number of participants with one or more TEAE, SAE and AESI.
Time frame: baseline through day 29(part 1)or day 106(part 2)
Area under the serum concentration versus time curve (AUC)
Area under the serum concentration versus time curve (AUC)
Time frame: baseline through day 29(part 1)or day 106(part 2)
Maximum observed serum concentration (Cmax)
Maximum observed serum concentration (Cmax)
Time frame: baseline through day 29(part 1)or day 106(part 2)
Time to reach maximum observed serum concentration (Tmax)
Time to reach maximum observed serum concentration (Tmax)
Time frame: baseline through day 29(part 1)or day 106(part 2)
Terminal elimination half-life (t1/2)
Terminal elimination half-life (t1/2)
Time frame: baseline through day 29(part 1)or day 106(part 2)
Mean residence time (MRT)
Mean residence time (MRT)
Time frame: baseline through day 29(part 1)or day 106(part 2)
Apparent clearance after extravascular administration (CL/F)
Apparent clearance after extravascular administration (CL/F)
Time frame: baseline through day 29(part 1)or day 106(part 2)
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Apparent volume of distribution during the terminal elimination phase after extravascular administration (Vz/F)
Apparent volume of distribution during the terminal elimination phase after extravascular administration (Vz/F)
Time frame: baseline through day 29(part 1)or day 106(part 2)
AUC from time 0 to the time of the dosing interval (AUC0-t)
AUC from time 0 to the time of the dosing interval (AUC0-t)
Time frame: baseline through day 106(part 2)
Accumulation ratio (AR)
Accumulation ratio (AR)
Time frame: baseline through day 106(part 2)
Predose concentrations(Ctrough)
Predose concentrations(Ctrough)
Time frame: baseline through day 106(part 2)
change in body weight
change in body weight
Time frame: baseline through Day 85
change in adiponectin
change in adiponectin
Time frame: baseline through Day 85
change in BMI
change in BMI
Time frame: baseline through Day 85
change in waist circumference
change in waist circumference
Time frame: baseline through Day 85
change in fasting lipid profile
change in fasting lipid profile
Time frame: baseline through Day 85
change in fasting plasma glucose (FPG)
change in FPG
Time frame: baseline through Day 85
change in HbA1c
change in HbA1c
Time frame: baseline through Day 85
change in C-peptide
change in C-peptide
Time frame: baseline through Day 85
change in fasting insulin
change in fasting insulin
Time frame: baseline through Day 85
change in glucagon
change in glucagon
Time frame: baseline through Day 85
change in homeostatic model assessment index of insulin resistance (HOMA-IR) and homeostatic model assessment index of beta-cell function (HOMA-B)
change in HOMA-IR and HOMA-B
Time frame: baseline through Day 85
change in Partial area glucose level versus time curve from time 0 to 4 hours (△AUC0-4h)
change in Partial area glucose levels versus time curve from time 0 to 4 hours (△AUC0-4h)
Time frame: baseline through Day 85
change in Partial area insulin level versus time curve from time 0 to 4 hours (△AUC0-4h)
change in Partial area insulin levels versus time curve from time 0 to 4 hours (△AUC0-4h)
Time frame: baseline through Day 85
change in Partial area C-peptide level versus time curve from time 0 to 4 hours (△AUC0-4h)
change in Partial area C-peptide levels versus time curve from time 0 to 4 hours (△AUC0-4h)
Time frame: baseline through Day 85
change in Partial area glucagon level versus time curve from time 0 to 4 hours (△AUC0-4h)
change in Partial area glucagon levels versus time curve from time 0 to 4 hours (△AUC0-4h)
Time frame: baseline through Day 85
change percentage of time spent of glucose in target range 3.9 to 10 mmol/L (TIR), time above target range (TAR), time below target range (TBR), 24-hour mean glucose, and glucose variability
change in TIR, TAR, TBR, 24-hour mean glucose, and glucose variability
Time frame: baseline through Day 85
change in hepatic fat fraction measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF ) in part 2
change in hepatic fat fraction measured by MRI-PDFF in part 2
Time frame: baseline through Day 85
Change in liver stiffness by FibroScan in subjects with baseline hepatic fat of at least 8%
Change in liver stiffness by FibroScan in subjects with baseline hepatic fat of at least 8%
Time frame: baseline through Day 85
Change in the liver function parameters (ALT, AST, alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT))
Change in the liver function (ALT, AST, alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT))
Time frame: baseline through Day 85
Change in Fibrosis 4 score (FIB-4) and non-alcoholic fatty liver disease fibrosis score (NFS)
Change in FIB-4 and NFS
Time frame: baseline through Day 85