Evaluation of the effects of bitopertin (RG1678) on cardiac repolarization: a thorough corrected QT study in healthy male volunteers
Abstract
BACKGROUND: Bitopertin (RG1678) is a selective glycine reuptake inhibitor currently in Phase III development for the treatment of schizophrenia. Thorough QT studies to assess the effects of candidate drugs on cardiac repolarization and proarrhythmic potential are required by regulatory authorities and are a common part of the drug development process. A clinically relevant effect on QT interval is suspected if prolongation of the corrected QT interval (QTc) is ∼5 milliseconds or more, evidenced by an upper 1-sided 95% CI for the mean effect on the QTc of at least 10 milliseconds.
OBJECTIVE: The goal of this study was to investigate the effect of bitopertin on the QTc interval in healthy male volunteers.
METHODS: This was a multiple-dose, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study using bitopertin 30 mg (n = 56) or bitopertin 175 mg (n = 56) once daily for 10 days plus placebo on day 11, moxifloxacin 400 mg on day 1 plus placebo once daily for 10 days (n = 29), or placebo once daily for 10 days plus moxifloxacin 400 mg on day 11 (n = 28). Continuous Holter ECGs were obtained on days -1, 1, 10, and 11, and the placebo-corrected mean change from time-matched baseline in the QT interval calculated by using Fridericia's formula (QTcF) on day 10 was the primary end point. Pharmacokinetic parameters of bitopertin were determined on day 10 by using HPLC-MS/MS methods to obtain bitopertin plasma drug concentrations. Adverse events were recorded…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 56 participants or records.
Read the paper
Related studies
- Synthesis, In Vitro and In Silico Molecular Docking Studies of Novel Phthalimide–Pyrimidine Hybrid Analogues to Thalidomide as Potent Antitubercular Agents
- Exploring the inhibitory performance of expired moxifloxacin and norfloxacin on copper corrosion in saline environment
- Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach
- Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches
- Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.