Assessment of drug–drug interaction potential with EDP‐305, a farnesoid X receptor agonist, in healthy subjects
Abstract EDP‐305 is a farnesoid X receptor (FXR) agonist that selectively activates FXR and is a potential treatment for patients with nonalcoholic steatohepatitis (NASH) with liver fibrosis. Results from preclinical studies indicate that CYP3A4 is the primary enzyme involved in EDP‐305 metabolism a...
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| Format: | Article |
| Language: | English |
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Wiley
2022-09-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13348 |
| _version_ | 1811261261496713216 |
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| author | Alaa Ahmad Nathalie Adda |
| author_facet | Alaa Ahmad Nathalie Adda |
| author_sort | Alaa Ahmad |
| collection | DOAJ |
| description | Abstract EDP‐305 is a farnesoid X receptor (FXR) agonist that selectively activates FXR and is a potential treatment for patients with nonalcoholic steatohepatitis (NASH) with liver fibrosis. Results from preclinical studies indicate that CYP3A4 is the primary enzyme involved in EDP‐305 metabolism and that EDP‐305 has low potential to inhibit or induce cytochrome (CYP) isoenzymes and drug transporters. Four studies were conducted in healthy volunteers to evaluate the drug–drug interaction (DDI) potential of EDP‐305 co‐administered with drugs known to be substrates for drug metabolizing enzymes or transporters, and to assess the effect of inhibitors and inducers of CYP3A4 on EDP‐305. Results suggest caution when substrates of CYP3A4 are administered concomitantly with EDP‐305. A potential for increased exposure is apparent when CYP1A2 substrates with a narrow therapeutic index are administered with EDP‐305. In contrast, substrates of drug transporters can be administered concomitantly with EDP‐305 with a low potential for interactions. Coadministration of EDP‐305 and a combined OC had no relevant effects on plasma concentrations of the combined OC. Co‐administration of EDP‐305 with strong or moderate inhibitors and inducers of CYP3A4 is not recommended. These results indicate low overall likelihood of interaction of EDP‐305 and other substrates through CYP mediated interactions. The interaction potential of EDP‐305 with drug transporters was low and of unlikely clinical significance. The EDP‐305 DDI profile allows for convenient administration in patients with NASH and other patient populations with comorbidities, with minimal dose modification of concomitant medications. |
| first_indexed | 2024-04-12T19:01:21Z |
| format | Article |
| id | doaj.art-bc536bf0dc9f421caeca28d623ba23f8 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-04-12T19:01:21Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-bc536bf0dc9f421caeca28d623ba23f82022-12-22T03:20:09ZengWileyClinical and Translational Science1752-80541752-80622022-09-011592146215810.1111/cts.13348Assessment of drug–drug interaction potential with EDP‐305, a farnesoid X receptor agonist, in healthy subjectsAlaa Ahmad0Nathalie Adda1Enanta Pharmaceuticals Inc. Watertown Massachusetts USAEnanta Pharmaceuticals Inc. Watertown Massachusetts USAAbstract EDP‐305 is a farnesoid X receptor (FXR) agonist that selectively activates FXR and is a potential treatment for patients with nonalcoholic steatohepatitis (NASH) with liver fibrosis. Results from preclinical studies indicate that CYP3A4 is the primary enzyme involved in EDP‐305 metabolism and that EDP‐305 has low potential to inhibit or induce cytochrome (CYP) isoenzymes and drug transporters. Four studies were conducted in healthy volunteers to evaluate the drug–drug interaction (DDI) potential of EDP‐305 co‐administered with drugs known to be substrates for drug metabolizing enzymes or transporters, and to assess the effect of inhibitors and inducers of CYP3A4 on EDP‐305. Results suggest caution when substrates of CYP3A4 are administered concomitantly with EDP‐305. A potential for increased exposure is apparent when CYP1A2 substrates with a narrow therapeutic index are administered with EDP‐305. In contrast, substrates of drug transporters can be administered concomitantly with EDP‐305 with a low potential for interactions. Coadministration of EDP‐305 and a combined OC had no relevant effects on plasma concentrations of the combined OC. Co‐administration of EDP‐305 with strong or moderate inhibitors and inducers of CYP3A4 is not recommended. These results indicate low overall likelihood of interaction of EDP‐305 and other substrates through CYP mediated interactions. The interaction potential of EDP‐305 with drug transporters was low and of unlikely clinical significance. The EDP‐305 DDI profile allows for convenient administration in patients with NASH and other patient populations with comorbidities, with minimal dose modification of concomitant medications.https://doi.org/10.1111/cts.13348 |
| spellingShingle | Alaa Ahmad Nathalie Adda Assessment of drug–drug interaction potential with EDP‐305, a farnesoid X receptor agonist, in healthy subjects Clinical and Translational Science |
| title | Assessment of drug–drug interaction potential with EDP‐305, a farnesoid X receptor agonist, in healthy subjects |
| title_full | Assessment of drug–drug interaction potential with EDP‐305, a farnesoid X receptor agonist, in healthy subjects |
| title_fullStr | Assessment of drug–drug interaction potential with EDP‐305, a farnesoid X receptor agonist, in healthy subjects |
| title_full_unstemmed | Assessment of drug–drug interaction potential with EDP‐305, a farnesoid X receptor agonist, in healthy subjects |
| title_short | Assessment of drug–drug interaction potential with EDP‐305, a farnesoid X receptor agonist, in healthy subjects |
| title_sort | assessment of drug drug interaction potential with edp 305 a farnesoid x receptor agonist in healthy subjects |
| url | https://doi.org/10.1111/cts.13348 |
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