A Randomized, Double-Blinded, Placebo-Controlled QTc Study to Evaluate BIA 28-6156 Effect on Cardiac Repolarization in Healthy Volunteers.
Phase 1 randomized crossover thorough QTc study in 37 healthy volunteers found BIA 28-6156, an allosteric GCase activator for GBA-associated Parkinson’s, produced no clinically relevant QTc prolongation and was generally well tolerated.
What the AI sees
Phase 1 randomized crossover thorough QTc study in 37 healthy volunteers found BIA 28-6156, an allosteric GCase activator for GBA-associated Parkinson’s, produced no clinically relevant QTc prolongation and was generally well tolerated.
Research significance
By demonstrating cardiac safety and tolerability of a GBA-targeted small molecule, this de-risks further clinical development of a potentially disease-modifying therapy for GBA-associated PD and supports progression to efficacy trials.
Source abstract
Mutations in the GBA1 gene, encoding beta-glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson's Disease (PD). BIA 28-6156, an allosteric activator of GCase, is under development for the treatment of GBA-associated PD. This Phase 1, randomized, double-blind, placebo-controlled, crossover study assessed the impact of BIA 28-6156 on QT interval corrected (QTc) for heart rate (HR) based on the Fridericia correction (QTcF) in 37 healthy subjects. Participants received single doses of 60 or 150 mg BIA 28-6156, 400 mg moxifloxacin, or placebo in a cross-over design. The relationship between BIA 28-6156 plasma levels and QTcF changes (ΔQTcF) was analyzed to exclude a ΔΔQTcF > 10 ms. Heart rate, PR, and QRS intervals, electrocardiogram (ECG) waveform morphology, and adverse events (AEs) were also evaluated. The concentration-QTc analysis indicated no effect on ΔΔQTcF exceeding 10 ms up to BIA 28-6156 plasma levels of ≈7150 ng/mL. No clinically significant effects on ECG parameters were observed, and BIA 28-6156 was generally well tolerated, with no deaths or serious AEs. This study concluded that BIA 28-6156 has no clinically relevant impact on ECG parameters, confirming a negative thorough QT/QTc study.