enerisant (TS-091) / Taisho - LARVOL DELTA

How to Measure Uncertainty in Laboratory Tests (ISLH 2024) - "In 2019, ISO released ISO/TS20914 [2] and this was hailed as the guidance that was needed...9, pp. 1447-1457, 2018."

Cardiovascular • Hematological Disorders • Thrombosis

Optimal dose determination of enerisant (TS-091) for patients with narcolepsy: two randomized, double-blind, placebo-controlled trials. (PubMed, BMC Psychiatry) - P2 | "The optimal dose of enerisant could not be determined in these two studies. Although enerisant has a favorable pharmacokinetic profile, it is thought to have large interindividual variabilities in terms of efficacy and safety, suggesting the necessity of tailored dosage adjustments."

Clinical • Journal • CNS Disorders • Excessive Daytime Sleepiness • Insomnia • Narcolepsy • Pain • Sleep Disorder

Pharmacokinetic and pharmacodynamic assessment of histamine H receptor occupancy by enerisant: a human PET study with a novel H binding ligand, [C]TASP457. (PubMed, Eur J Nucl Med Mol Imaging) - P1 | "The target engagement of enerisant was demonstrated in the brains of living human subjects. The occupancy of histamine H receptors by enerisant at 2 h can be predicted by applying the plasma concentration of enerisant to Hill's plot. The preliminary time-course investigation showed persistently high brain occupancy with high doses of enerisant despite the decreasing plasma concentration of the drug. Five milligrams or less dose would be appropriate for the treatment for narcolepsy with initially high occupancy allowing for effective treatment of narcolepsy, and then the occupancy level would be expected to decrease to a level to avoid this drug's unwanted side effect of insomnia at night, although further research is warranted to confirm the statement since the expected decrease is based on the finding in one subject."

Journal • PK/PD data • CNS Disorders • Insomnia • Narcolepsy • Sleep Disorder

Drug-drug interaction potential and clinical pharmacokinetics of enerisant, a novel potent and selective histamine H receptor antagonist. (PubMed, Xenobiotica) - "The urinary excretion of enerisant within 48 h after administration was 64.5% to 89.9% of the dose, indicating that most of the absorbed enerisant was excreted in the urine without being metabolized.Based on the plasma concentrations at the estimated clinical dose, enerisant is unlikely to cause CYP-mediated, clinically relevant DDI. Although the possibility of transporter-mediated, clinically relevant DDI cannot be ruled out, there is little or no risk of side effects."

Clinical • Journal • PK/PD data • Breast Cancer • Oncology • Solid Tumor • CYP2C19 • CYP2C8 • CYP2C9 • CYP2E1 • CYP3A4

Clinical Study on Histamine H3 Receptor Occupancy of TS-091 by PET Examination in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=12; Completed; Sponsor: Taisho Pharmaceutical Co., Ltd.

Clinical • New P1 trial

A Novel Potent and Selective Histamine H3 Receptor Antagonist Enerisant: In Vitro Profiles, In Vivo Receptor Occupancy, Wake-Promoting and Pro-cognitive Effects in Rodents. (PubMed, J Pharmacol Exp Ther) - "Significance Statement Enerisant is a novel histamine H3 receptor antagonist/inverse agonist that exerts wake-promoting and pro-cognitive effects in addition to increasing the release of neurotransmitters related to these pharmacological effects in rodents. Moreover, an in vivo receptor binding study revealed that the in vivo occupancy of the histamine H3 receptor required to exert the pharmacological effects of enerisant varied, and such variations in required occupancy should be taken into account when performing dose selection in clinical studies."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders

A Study to Evaluate the Safety and Efficacy of TS-091 in Patients With Narcolepsy (clinicaltrials.gov) - P2; N=53; Completed; Sponsor: Taisho Pharmaceutical Co., Ltd.; Active, not recruiting ➔ Completed; Trial completion date: Mar 2019 ➔ Aug 2019

Clinical • Trial completion • Trial completion date