No QTcF Prolongation with Sepiapterin: Results From a Thorough QT Study in Healthy Subjects at Therapeutic and Supratherapeutic Doses.

ABSTRACT: Sepiapterin and its major metabolite 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH₄) bind to distinct variants of phenylalanine hydroxylase (PAH), which converts excess phenylalanine to tyrosine, thereby stabilizing, enhancing, and prolonging PAH activity. Sepiapterin was recently approved in Europe and the USA for the treatment of hyperphenylalaninemia patients with phenylketonuria, an inherent metabolic disease caused by PAH deficiency. A thorough QT study of sepiapterin in healthy volunteers at therapeutic (60 mg/kg) and supratherapeutic (120 mg/kg) doses was conducted to assess potential cardiovascular risks. Thirty-two participants were randomized into one of 12 sequences and received single doses of sepiapterin (60 or 120 mg/kg), moxifloxacin 400 mg, or placebo in separate

SUBMITTER: Gao L 

PROVIDER: S-EPMC12801174 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature