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Published on: September 18, 2013
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LY3522348, A New Ketohexokinase Inhibitor: A First-in-Human Study in Healthy Adults
Tsuyoshi Fukuda1, Brian R Thompson1, Bram Brouwers1
1Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Summary
The ketohexokinase inhibitor LY3522348 showed a favorable safety profile and predictable pharmacokinetics in healthy adults. This oral medication effectively inhibited fructose metabolism, demonstrating its potential therapeutic value.
Area of Science:
- Pharmacology
- Metabolic Diseases
- Drug Development
Background:
- Ketohexokinase (KHK) plays a crucial role in fructose metabolism.
- Inhibiting KHK is a potential therapeutic strategy for metabolic disorders.
- LY3522348 is a novel, selective oral dual inhibitor of KHK isoforms C and A.
Purpose of the Study:
- To assess the safety and tolerability of single and multiple doses of LY3522348.
- To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of LY3522348.
- To evaluate potential drug-drug interactions of LY3522348.
Main Methods:
- Phase 1, first-in-human study with healthy participants.
- Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) parts.
- Doses ranged from 5-380 mg (SAD) and 50-290 mg daily (MAD) for 14 days.
Main Results:
- LY3522348 was well-tolerated with predominantly mild adverse events.
- PK analysis revealed dose-proportional increases in exposure with a half-life of 23.7-33.8 hours.
- PD analysis showed dose-dependent increases in plasma fructose, confirming KHK inhibition.
Conclusions:
- LY3522348 exhibits a favorable safety profile and predictable PK with once-daily oral dosing.
- The drug effectively inhibits fructose metabolism.
- Further investigation into LY3522348 is warranted.
