Safety, Pharmacokinetics, Pharmacodynamics, and Formulation of Liver‐Distributed Farnesoid X‐Receptor Agonist TERN‐101 in Healthy Volunteers

TERN‐101 is a nonsteroidal farnesoid X‐receptor agonist being developed for the treatment of nonalcoholic steatohepatitis (NASH). We assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TERN‐101 capsule and tablet formulations in healthy volunteers. In a randomized, double‐blind,...

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Veröffentlicht in:Clinical pharmacology in drug development 2021-10, Vol.10 (10), p.1198-1208
Hauptverfasser: Wang, Yujin, Crittenden, Daria B., Eng, Clarence, Zhang, Qiong, Guo, Pengfei, Chung, Diana, Fenaux, Martijn, Klucher, Kevin, Jones, Christopher, Jin, Feng, Quirk, Erin, Charlton, Michael R.
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Sprache:eng
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Zusammenfassung:TERN‐101 is a nonsteroidal farnesoid X‐receptor agonist being developed for the treatment of nonalcoholic steatohepatitis (NASH). We assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TERN‐101 capsule and tablet formulations in healthy volunteers. In a randomized, double‐blind, placebo‐controlled study, 38 participants were enrolled and randomized to receive placebo or 25‐, 75‐, or 150‐mg TERN‐101 capsules orally once daily for 7 days. In a separate open‐label PK and formulation‐bridging study, 16 participants received single doses of TERN‐101 tablets (5 and 25 mg) or capsules (25 mg). TERN‐101 was overall well‐tolerated in this healthy volunteer population; no pruritus was reported. TERN‐101 capsule administration over 7 days resulted in decreases in serum 7α‐hydroxy‐4‐cholesten‐3‐one that were sustained for 24 hours after the last dose (maximum suppression 91% from baseline), indicating target engagement in the liver. TERN‐101 capsules exhibited less than dose‐proportional PK. Relative to capsules, TERN‐101 tablets showed increased bioavailability, with 24‐hour plasma exposure of the 5‐mg tablet similar to that of the 25‐mg capsule. There was no significant effect of food on exposure. The overall safety, PK, and PD profiles of TERN‐101 support its further evaluation for the treatment of NASH.
ISSN:2160-763X
2160-7648
DOI:10.1002/cpdd.960