Non‐clinical and first‐in‐human characterization of ECC5004 / AZD5004 , a novel once‐daily, oral small‐molecule GLP ‐1 receptor agonist
Authors' conclusion
ECC5004 engaged the GLP-1R across the therapeutic dose range tested and had a safety and tolerability profile consistent with other GLP-1 RAs, along with a pharmacokinetic profile compatible with once-daily oral dosing. These data support continued development of ECC5004 as a potential therapy for T2DM and overweight or obesity.
Study context
- Population
- Cell lines overexpressing human GLP-1R, human β-cell line, non-human primates (NHPs); healthy volunteers (single doses) and patients with T2D (multiple doses)
- Comparison
- ECC5004 vs placebo
- Outcome
- Non-clinical pharmacology
Methodological detailsnon-clinical and first-in-human, phase I, double-blind, placebo-controlled, single and multiple ascending doses
- Non-clinical and first-in-human
- Phase I
- Double-blind
- Placebo-controlled
- Single and multiple ascending doses
Main finding
As reported in the abstract
Binding to hGLP-1R, IC50
2.4 nM
Potentiation of glucose-stimulated insulin secretion (GSIS) in EndoC-βH5 cells, EC50
5.9 nM
Potentiation of GSIS in vivo in NHPs, EC50
0.022 nM
Further findings
Glucose and body weight in first-in-human (FIH) study
- Dose-dependent reductions in glucose and body weight
- Dose-proportional exposure at doses ≥25 mg
Body weight, 9-month NHP toxicity study
- Dose-dependent body weight changes vs control
Safety
Safety and tolerability, FIH study
- Serious adverse events
- 0
- Well tolerated
Original publication
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