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Clinical development of tricaprilin, a ketogenic drug for Alzheimer's disease
Author(s) -
Walker Judith Anne,
Nelleman Lars,
Henderson Samuel T,
Morimoto Bruce
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.038787
Subject(s) - tolerability , medicine , pharmacokinetics , drug , disease , pharmacology , dementia , in vivo , ketosis , endocrinology , adverse effect , biology , diabetes mellitus , microbiology and biotechnology
Background Cerebral glucose hypometabolism in posterior cingulate, parietal, temporal, and prefrontal cortex is an early feature of Alzheimer’s disease (AD). Cells in these regions which exhibit a defect in glucose metabolism have been shown to preserve the ability to metabolise ketones. We report on an approach to induce ketosis and treat AD with a new drug formulation of a semi‐synthetic triglyceride, tricaprilin. Method Novel formulations of tricaprilin were developed and tested in vitro, in vivo, and in human studies to assess pharmacokinetics, safety, and tolerability. The clinical studies were conducted in healthy human Caucasian and Asian volunteers and in a variety of food conditions. Result Two new formulations of tricaprilin showed desirable PK characteristics, leading to generation of ketones and excellent safety and tolerability, when administered in doses of 20g after a meal, in both Caucasians and Asians. Conclusion The selected formulation will be moved forward in drug development with an ascending dose study in healthy elderly subjects and a Phase 3 study in mild to moderate Alzheimer's disease.