Hydrobromide Salt Formulation Sample Clauses

Hydrobromide Salt Formulation. An analysis of chloride levels in subjects on Study EZH-102 at the 1200 mg/m2 dose level showed elevated chloride levels (beyond the ULN) in 5/7 subjects who had been treated at this dose level. Reviewing this finding further, subjects at lower dose levels (4/6 subjects at 900 mg/m2, 4/6 subjects at 700mg/m2 and 4/6 subjects at 520 mg/m2) also demonstrated elevated chloride levels. Hyperchloremia is considered an artifact resulting from interference of serum bromide with the serum chloride assay (tazemetostat is a bromide salt). Artifactually elevated serum chloride was also noted in repeat-dose nonclinical toxicology studies of tazemetostat in rats and monkeys at tazemetostat doses up to 1000 mg/kg/day. Ion exchange chromatography showed increased serum chloride in these nonclinical studies to be pseudo-hyperchloremia, representing increased bromide. Bromide levels were measured in the Phase 1 study of tazemetostat in adults. Bromide was within normal levels (<6.2 mmol/L) for all subjects taking the oral tablet formulation in doses up to 1600 mg BID. However, mean tazemetostat AUC(0-24) in children at the 1200 mg/m2 dose level exceeded that observed in the 1600 mg BID dose group in adults from Study E7438- G000-101. Therefore, the assessment of bromide levels was instituted in Amendment No. 5 for all active and new subjects. Refer to Section 8.5.10 and Table 11 for the schedule of bromide level assessments and to Section 6.5.2 for dose modifications due to bromide toxicity. The chloride assay is being collected locally at every visit as part of the electrolyte panel, which is included in the standard blood chemistry assessment (Table 11). For more details, refer to the tazemetostat Investigator’s Brochure, Version 10.0.