A Randomized, Double‐Blinded, Placebo‐Controlled QTc Study to Evaluate BIA 28–6156 Effect on Cardiac Repolarization in Healthy Volunteers

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Healthy Volunteers (n=37). Intervention: BIA 28-6156 vs. Placebo. Primary outcome: Predicted placebo-corrected change from baseline in QTcF (ΔΔQTcF) at the geometric mean peak plasma concentration of the 150 mg dose (MD 0.41 ms, 95% CI -1.00 to 1.82).

Q: What does this research mean for the field?

The GCase activator BIA 28-6156 does not cause clinically significant prolongation of the QTc interval or other relevant ECG changes in healthy volunteers at plasma levels up to approximately 7150 ng/mL. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Isa Peixoto; Dana Hilt; Teresa Carvalho; João Gabbardo dos Reis; Helena Gama; J. Holenz

doi:10.1002/cpdd.70055

April 1, 2026Clinical Pharmacology in Drug DevelopmentOpen Access

A Randomized, Double‐Blinded, Placebo‐Controlled QTc Study to Evaluate BIA 28–6156 Effect on Cardiac Repolarization in Healthy Volunteers

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Key result

Single therapeutic and supratherapeutic doses of BIA 28-6156 did not produce any clinically relevant prolongation of the QTc interval, successfully excluding an effect exceeding 10 ms.

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Why the study?

BIA 28-6156 is under development for the treatment of GBA-associated Parkinson's disease, requiring assessment of its impact on cardiac repolarization.

Does single-dose BIA 28-6156 cause clinically significant QTcF interval prolongation compared to placebo in healthy volunteers?

Key Points

To assess the effect of single therapeutic (60 mg) and supratherapeutic (150 mg) doses of BIA 28-6156 on cardiac repolarization in healthy participants.
Phase 1, randomized, double-blind, placebo-controlled crossover study enrolled 37 healthy subjects (17 females, 20 males; mean age 37 years).
Participants received single doses of 60 mg BIA 28-6156, 150 mg BIA 28-6156, 400 mg moxifloxacin (positive control), or placebo.
Cardiac repolarization was assessed via Fridericia-corrected QT interval (QTcF) using concentration-QTc modeling to rule out a placebo-corrected change from baseline (ΔΔQTcF) greater than 10 ms.
Predicted ΔΔQTcF effects at geometric mean peak plasma concentrations were 0.13 ms (90% CI: -0.61 to 0.87) for 60 mg and 0.41 ms (90% CI: -1.00 to 1.82) for 150 mg, excluding a ΔΔQTcF > 10 ms up to ~7150 ng/mL.
Assay sensitivity was confirmed with moxifloxacin, demonstrating a predicted QT effect of 10.20 ms (90% CI: 8.33 to 12.07) at peak plasma concentration and a maximum mean ΔΔQTcF of 11.4 ms at 4 h post-dose.
Treatment-emergent adverse events occurred in 24 of 37 subjects (64.9%), with drug-related events reported in 5 subjects (13.5%) and no serious adverse events or deaths.

Study Design

Type

RCT (n=37)

Blinding

Double-blind

Randomization

Randomized to 1 of 12 treatment sequences

Structured PICO

Does single-dose BIA 28-6156 cause clinically significant QTcF interval prolongation compared to placebo in healthy volunteers?

P

Population

37 healthy adults aged 18 to 55 years were randomized in a crossover design to single doses of BIA 28-6156, moxifloxacin, or placebo to evaluate effects on cardiac repolarization.

I

Intervention

BIA 28-6156 as single oral doses of 60 mg (therapeutic) or 150 mg (supratherapeutic) administered in the fed state.

C

Comparator

Matching placebo capsules and active comparator moxifloxacin 400 mg oral capsules administered in a 4-period crossover design.

O

Outcome

Placebo-corrected change in QTcF from baseline (ΔΔQTcF) analyzed via concentration-QTc modeling to exclude an effect exceeding 10 ms at the observed geometric mean maximum plasma concentration.safety

Main Result

Mean Difference: 0.41 (95% CI -1–1.82)

Limitations

Study was conducted in healthy, younger volunteers rather than the older target demographic with Parkinson's Disease who often present with comorbidities and polypharmacy.
Limited to single-dose administration rather than multiple dosing to steady-state.

Implication

Single therapeutic and supratherapeutic oral doses of BIA 28-6156, a GCase activator for Parkinson's disease, do not cause clinically relevant QTcF interval prolongation in healthy volunteers.

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.

Discussion

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Cite This Study

Peixoto et al. (2026) conducted an RCT in Healthy Volunteers (n=37). BIA 28-6156 vs. Placebo was evaluated on Predicted placebo-corrected change from baseline in QTcF (ΔΔQTcF) at the geometric mean peak plasma concentration of the 150 mg dose (MD 0.41 ms, 95% CI -1.00 to 1.82). Single therapeutic and supratherapeutic doses of BIA 28-6156 did not produce any clinically relevant prolongation of the QTc interval, successfully excluding an effect exceeding 10 ms.

synapsesocial.com/papers/69db37b04fe01fead37c5aca https://doi.org/10.1002/cpdd.70055

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A Randomized, Double‐Blinded, Placebo‐Controlled QTc Study to Evaluate BIA 28–6156 Effect on Cardiac Repolarization in Healthy Volunteers

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

A Randomized, Double‐Blinded, Placebo‐Controlled QTc Study to Evaluate BIA 28–6156 Effect on Cardiac Repolarization in Healthy Volunteers

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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