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Clinical Trial
. 2021 Oct;10(10):1198-1208.
doi: 10.1002/cpdd.960. Epub 2021 Jul 24.

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

Yujin Wang  1 , Daria B Crittenden  1 , Clarence Eng  1 , Qiong Zhang  1 , Pengfei Guo  1 , Diana Chung  1 , Martijn Fenaux  1 , Kevin Klucher  1 , Christopher Jones  1 , Feng Jin  1 , Erin Quirk  1 , Michael R Charlton  2
Affiliations
Clinical Trial

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

Yujin Wang et al. Clin Pharmacol Drug Dev. 2021 Oct.

Abstract

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.

Keywords: 7αC4; FGF19; FXR; NASH; liver.

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