Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (PEG)-BHD1028
NCT Number: NCT06563115
Status: COMPLETED
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Insulin Resistance
Interventions: DRUG: (PEG)-BHD1028 Single Ascending Dose|DRUG: (PEG)-BHD1028 Multiple Ascending Dose|OTHER: Placebo
Sponsor: EncuraGen, Inc
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 64
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2022-04-18
Completion Date: 2024-06-23
Locations: Altasciences Clinical, Overland Park, Kansas, 66212, United States

Summary:
Adiponectin has been known to play critical roles in various physio-regulatory processes, and adiponectin deficiency may contribute to insulin resistance. (PEG)-BHD1028 was developed as an agonist of adiponectin receptors.

This first-in-human study evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of (PEG)-BHD1028 in healthy overweight/obese subjects with insulin resistance.

Primary Outcome Measures: Safety and tolerability of (PEG)-BHD1028 -Single ascending dose as measured by TEAEs, Treatment emergent adverse events (including clinical AEs and Lab AEs) after a single dose of (PEG)-BHD1028 (including clinical AEs and Lab AEs) of (PEG)-BHD1028, Baseline to Day 3|Safety and tolerability of (PEG)-BHD1028 -Multiple ascending dose as measured by TEAEs, Treatment emergent adverse events (including clinical AEs and Lab AEs) after multiple doses of (PEG)-BHD1028, Baseline to Day 29
Secondary Outcome Measures: Pharmacokinetics of (PEG)-BHD1028 after a single dose, Cmax, Maximum plasma concentration of (PEG)-BHD1028, pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose|Pharmacokinetics of (PEG)-BHD1028 after a single dose, Tmax, Time to reach Maximum plasma concentration of (PEG)-BHD1028, pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose|Pharmacokinetics of (PEG)-BHD1028 after a single dose, t1/2, Time to reach apparent (PEG)-BHD1028 apparent terminal half life, pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose|Pharmacokinetics of (PEG)-BHD1028 after a single dose, AUClast, Area under the (PEG)-BHD1028 concentration -time curve up to the last measurable concentration in serum, pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose|Pharmacokinetics of (PEG)-BHD1028 after a single dose, AUCinf, AUCinf Area under the (PEG)-BHD1028 concentration -time curve up extrapolated to infinity, pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose|Pharmacokinetics of (PEG)-BHD1028 after a single dose, CL/F, CL/F Apparent clearance of the drug calculated as dose of drug divided by the AUC, pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose|Pharmacokinetics of (PEG)-BHD1028 after a single dose, Vd/F, Apparent Volume of distribution calculated as Total administered dose/initial plasma concentration, pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, Cmax, Maximum plasma concentration of (PEG)-BHD1028, pre-dose, and post dose on Day 1, Day 14 and Day 28|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, Tmax, Time to reach Maximum plasma concentration of (PEG)-BHD1028, pre-dose, and post dose on Day 1, Day 14 and Day 28|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, Cav,ss, Average plasma concentrate at steady state, pre-dose, and post dose on Day 1, Day 14 and Day 28|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, AUCtau, Area under the (PEG)-BHD1028 concentration -time curve up to the last dose, pre-dose, and post dose on Day 1, Day 14 and Day 28|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, t1/2, Time to reach (PEG)-BHD1028 apparent terminal half life, pre-dose, and post dose on Day 1, Day 14 and Day 28|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, CLss/F, Apparent plasma clearance of drug after extravascular administration at steady state, pre-dose, and post dose on Day 1, Day 14 and Day 28|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, Vd/F, Apparent volume of distribution after extravascular administration, pre-dose, and post dose on Day 1, Day 14 and Day 28|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, Rac(Cmax), Accumulation ratio calculated as Cmax (day 28)/ Cmax (day 1), post dose on Day 1 and Day 28|Pharmacokinetics of (PEG)-BHD1028 after multiple doses, Rac(AUC), Accumulation ratio calculated as AUC0-t (day 28)/ AUC0-t (day 1), post dose on Day 1 and Day 28|Pharmacodynamics of (PEG)-BHD 1028 after multiple doses as measured by Insulin C -peptide, Insulin c-peptide as assessed by the net AUC at baseline and the percentage change from baseline. Responders defined as subjects which exhibited a reduction in insulin c-peptide AUC during the Mixed Meal Tolerance Test (MMTT) of at least 15% from Day -1 to Day 28., Day -1 and Day 28|Pharmacodynamics of (PEG)-BHD 1028 after multiple doses as measured by insulin, Insulin AUC as assessed by the net AUC at baseline and the percentage change from baseline during the Mixed Meal Tolerance Test (MMTT)., Day -1 and Day 28|Pharmacodynamics of (PEG)-BHD 1028 after multiple doses as measured by glucose, Fasting plasma glucose (FPG), Post-prandial glucose (PPG), and glucose AUC assessed during the Mixed Meal Tolerance Test (MMTT)., Day -1 and Day 28