Pridopidine Does Not Significantly Prolong the QTc Interval at the Clinically Relevant Therapeutic Dose

Area of Science:

• Neuroscience
• Pharmacology
• Cardiology

Background:

• Pridopidine is a selective sigma-1 receptor (S1R) agonist developed for Huntington's disease (HD) and ALS.
• S1R activation by pridopidine supports neuronal function and survival, processes impaired in neurodegenerative conditions.
• PET imaging confirmed robust S1R occupancy by pridopidine at therapeutic doses.

Purpose of the Study:

• To assess the cardiac safety of pridopidine.
• To evaluate the effect of pridopidine on the QT interval using concentration-QTc (C-QTc) analysis.
• To investigate cardiac-related adverse events (AEs) associated with pridopidine treatment.

Main Methods:

• C-QTc analysis utilized data from the Phase 2 PRIDE-HD trial in 402 HD patients.
• Electrocardiograms (ECGs) and plasma drug concentrations were collected to assess the Fridericia-corrected QT interval (QTcF).
• Cardiac AEs were analyzed from PRIDE-HD and pooled data from three double-blind, placebo-controlled HD trials.

Main Results:

• A concentration-dependent effect of pridopidine on QTcF was observed.
• At the therapeutic dose (45 mg bid), the predicted placebo-corrected ΔQTcF was 6.6 ms, below the level of clinical concern.
• Cardiac AE frequencies were similar to placebo in pooled HD trials; no patients experienced QTcF ≥ 500 ms or Torsade de Pointes.

Conclusions:

• Pridopidine exhibits a favorable cardiac safety profile at the therapeutic dose of 45 mg bid.
• The observed effect on the QTc interval is not clinically relevant.
• Pridopidine is a potentially safe treatment option for HD and ALS.