Phase 1 Clinical Results for NP10679, a pH-sensitive GluN2B-selective N-methyl-d-aspartate Receptor Inhibitor

Area of Science:

• Neuroscience
• Pharmacology
• Clinical Trials

Background:

• N-methyl-D-aspartate (NMDA) receptors play a crucial role in neurological function and dysfunction.
• Developing subunit-selective NMDA receptor modulators is a key strategy for treating neurological disorders.
• NP10679 is designed as a context-dependent and subunit-selective negative allosteric modulator targeting GluN2B-containing NMDA receptors.

Purpose of the Study:

• To evaluate the pharmacokinetics and safety of NP10679 in healthy human volunteers.
• To determine the tolerability and side effect profile of single and multiple doses of NP10679.
• To assess the suitability of NP10679 for further clinical development.

Main Methods:

• A first-in-human Phase 1 clinical trial (NCT04007263) was conducted.
• Healthy volunteers received single or multiple doses of NP10679.
• Pharmacokinetic parameters, safety, and tolerability were assessed.

Main Results:

• NP10679 was found to be well-tolerated in healthy volunteers.
• The drug exhibited a half-life of 20 hours, supporting once-daily dosing.
• The primary side effect observed was mild somnolence at higher doses, with subjects easily aroused.

Conclusions:

• NP10679 demonstrates a favorable safety and pharmacokinetic profile in humans.
• Its subunit selectivity and context-dependent action suggest therapeutic potential.
• NP10679 is a candidate for further development in acute brain injury and neuropsychiatric indications.