Safety, Tolerability, and Pharmacokinetics of Valemetostat Tablets and the Effect of Food on Valemetostat Pharmacokinetics in Healthy Subjects: Two Phase 1 Studies

We report outcomes from 2 phase 1 trials in healthy Japanese participants, assessing the safety, tolerability, and pharmacokinetics (PK) of valemetostat tablets at single ascending doses (50, 100, and 200-mg), the relative bioavailability between capsules and tablets, and the effect of food (high-fat or low-fat meals) on the PK of valemetostat tablets. In the ascending-dose study, valemetostat maximum plasma concentration (Cmax) and area under the concentration –time curve (AUC) increased dose-proportionally. Valemetostat plasma PK parameters were similar between the capsule and tablet formulations following a single 200-mg dose. Administration of valemetostat, 200 mg after a meal, was associated with 50%-60% lower Cmax, 30%-50% lower AUC, and a median Tmax delay of 2.5-3  hours relative to fasted administration. Valemetostat was well tolerated in healthy subjects; treatment-emergent adverse events were mild (grade 1) in severity. Based on these trials, the tablet formulation of valemetostat is suitable for use in subsequent clinical trials and should be administere d under fasted conditions to avoid a negative food effect.
Source: Clinical Pharmacology in Drug Development - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research