To assess the pharmacokinetics following administration of a single oral dose of fosigotifator granules in the fed state compared to fasted state and assess the acceptability of administration with soft foods

Fosigotifator is a small molecule activator of eIF2B, the guanine nucleotide exchange factor for eukaryotic translation initiation factor (eIF2). eIF2 is an important node in the Integrated Stress Response (ISR), a pathway implicated in the pathophysiology of several neurological conditions, including Amyotrophic Lateral Sclerosis (ALS, NCT05740813) and Vanishing White Matter (VWM, NCT05757141) disease. To inform administration after a high-fat meal or with soft foods, a food effect study was conducted.

This was a Phase 1, single-dose, randomized, three-period, six sequence crossover study. Eighteen adult subjects in general good health were selected to participate in the study. Serial PK was collected and PK parameters were obtained by noncompartmental analyses.

In-use study was conducted to determine the stability, compatibility, and dose preparation procedure repeatability of various soft foods.

Following administration in the fed state, C_max was approximately 30% lower compared to administration in the fasting state, and there was no effect on AUC. This difference in C_max is not considered to be clinically meaningful. Following administration with or without applesauce, C_max and AUC were comparable.

No clinically significant patterns in adverse events or vital sign, laboratory, C-SSRS, and ECG parameters were observed during the course of the study.

Based on the analytical results obtained for stability, recovery, and dose preparation repeatability applesauce, yogurt, cream cheese, and strawberry jam are compatible and qualified to be used as dosing vehicles for administration of fosigotifator.

Fosigotifator may be administered without regard to food and may be administered with various soft foods such as applesauce, yogurt, cream cheese, and strawberry jam.