Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia.

Background: Hydromethylthionine is a potent inhibitor of pathological aggregation of tau and TDP-43 proteins.

Objective: To compare hydromethylthionine treatment effects at two doses and to determine how drug exposure is related to treatment response in bvFTD.

Methods: We undertook a 52-week Phase III study in 220 bvFTD patients randomized to compare hydromethylthionine at 200 mg/day and 8 mg/day (intended as a control).

Concentration-Dependent Activity of Hydromethylthionine on Cognitive Decline and Brain Atrophy in Mild to Moderate Alzheimer's Disease.

Background: Although hydromethylthionine is a potent tau aggregation inhibitor, no difference was found in either of two Phase III trials in mild to moderate Alzheimer's disease (AD) comparing doses in the range 150-250 mg/day with 8 mg/day intended as a control.

Objective: To determine how drug exposure is related to treatment response.

Methods: A sensitive plasma assay for the drug was used in a population pharmacokinetic analysis of samples from 1,162 of the 1,686 patients who participated in either of the Phase III trials with available samples and efficacy outcome data.