@article{10.11648/j.ijg.20210502.16,
  author = {Alaa Ahmad and Kristin Sanderson and Daniel Dickerson and Nathalie Adda},
  title = {Phase 1 Study of EDP-305, a Novel Once-Daily Oral Farnesoid X Receptor Agonist, in Healthy Subjects and Those with Presumptive Nonalcoholic Fatty Liver Disease},
  journal = {International Journal of Gastroenterology},
  volume = {5},
  number = {2},
  pages = {68-79},
  doi = {10.11648/j.ijg.20210502.16},
  url = {https://doi.org/10.11648/j.ijg.20210502.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijg.20210502.16},
  abstract = {Introduction: EDP-305 is a farnesoid X Receptor (FXR) agonist that selectively activates FXR and is currently under investigation for with the treatment of nonalcoholic steatohepatitis (NASH). The primary objective was to assess the safety of EDP-305 in healthy subjects and subjects with presumptive NAFLD. Methods: In this placebo-controlled double-blind Phase 1 study, healthy subjects (aged 20-55 years) were randomized to single or multiple oral doses of once daily EDP-305 or placebo and subjects with presumptive NAFLD (aged 25-52 years) were randomized to multiple oral doses of once daily EDP-305 or placebo for 14 days. Six cohorts received EDP-305 1 mg, 5 mg, 10 mg, 20 mg, 40 mg or 80 mg in the SAD phase including a food effect cohort that received EDP-305 10 mg. In the MAD phase, 12 cohorts received EDP-305 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg or 20 mg (six cohorts in healthy subjects and six in presumptive NAFLD). Results: In the SAD phase, 38 subjects received EDP-305 and 12 subjects received placebo, and in the MAD phase, 72 subjects received EDP-305 and 24 subjects received placebo. No serious adverse events were reported, and the most common treatment-emergent adverse events (TEAEs) in EDP-305 treated subjects were constipation, headache, and pruritus. The majority of TEAEs were mild to moderate in severity. EDP-305 exposure increased with single and multiple doses in both healthy subjects and those with presumptive NAFLD. EDP-305 exposure was approximately 3-fold higher in fed vs. fasted subjects. Strong FXR target engagement was demonstrated in both healthy and presumptive NAFLD subjects in the MAD phase with FGF19 increases and C4 reductions compared with placebo. Conclusion: EDP-305 was well tolerated, with pruritus the most common treatment-emergent adverse event at EDP-305 doses ≥10 mg and with minimal effects on lipids. Dose proportional PK support once daily dosing. Significant elevations of FGF19 and diminutions in C4 demonstrated potent engagement of the FXR receptor at doses that neither elicit adverse effects on lipids nor result in pruritus. These results supported further evaluation of EDP-305 in patients with NASH.},
 year = {2021}
}

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TY  - JOUR
T1  - Phase 1 Study of EDP-305, a Novel Once-Daily Oral Farnesoid X Receptor Agonist, in Healthy Subjects and Those with Presumptive Nonalcoholic Fatty Liver Disease
AU  - Alaa Ahmad
AU  - Kristin Sanderson
AU  - Daniel Dickerson
AU  - Nathalie Adda
Y1  - 2021/11/17
PY  - 2021
N1  - https://doi.org/10.11648/j.ijg.20210502.16
DO  - 10.11648/j.ijg.20210502.16
T2  - International Journal of Gastroenterology
JF  - International Journal of Gastroenterology
JO  - International Journal of Gastroenterology
SP  - 68
EP  - 79
PB  - Science Publishing Group
SN  - 2640-169X
UR  - https://doi.org/10.11648/j.ijg.20210502.16
AB  - Introduction: EDP-305 is a farnesoid X Receptor (FXR) agonist that selectively activates FXR and is currently under investigation for with the treatment of nonalcoholic steatohepatitis (NASH). The primary objective was to assess the safety of EDP-305 in healthy subjects and subjects with presumptive NAFLD. Methods: In this placebo-controlled double-blind Phase 1 study, healthy subjects (aged 20-55 years) were randomized to single or multiple oral doses of once daily EDP-305 or placebo and subjects with presumptive NAFLD (aged 25-52 years) were randomized to multiple oral doses of once daily EDP-305 or placebo for 14 days. Six cohorts received EDP-305 1 mg, 5 mg, 10 mg, 20 mg, 40 mg or 80 mg in the SAD phase including a food effect cohort that received EDP-305 10 mg. In the MAD phase, 12 cohorts received EDP-305 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg or 20 mg (six cohorts in healthy subjects and six in presumptive NAFLD). Results: In the SAD phase, 38 subjects received EDP-305 and 12 subjects received placebo, and in the MAD phase, 72 subjects received EDP-305 and 24 subjects received placebo. No serious adverse events were reported, and the most common treatment-emergent adverse events (TEAEs) in EDP-305 treated subjects were constipation, headache, and pruritus. The majority of TEAEs were mild to moderate in severity. EDP-305 exposure increased with single and multiple doses in both healthy subjects and those with presumptive NAFLD. EDP-305 exposure was approximately 3-fold higher in fed vs. fasted subjects. Strong FXR target engagement was demonstrated in both healthy and presumptive NAFLD subjects in the MAD phase with FGF19 increases and C4 reductions compared with placebo. Conclusion: EDP-305 was well tolerated, with pruritus the most common treatment-emergent adverse event at EDP-305 doses ≥10 mg and with minimal effects on lipids. Dose proportional PK support once daily dosing. Significant elevations of FGF19 and diminutions in C4 demonstrated potent engagement of the FXR receptor at doses that neither elicit adverse effects on lipids nor result in pruritus. These results supported further evaluation of EDP-305 in patients with NASH.
VL  - 5
IS  - 2
ER  - 

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