Work

Intranasal CBT101 demonstrates favorable safety and neurophysiological evidence of central activity in healthy male volunteers

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Objectives: CBT101 is a creatine prodrug under development for disorders driven by impaired neuronal energy homeostasis, with initial development focused on creatine transporter deficiency and amyotrophic lateral sclerosis. This first-in-human study aimed to assess the safety and tolerability of single and repeated ascending intranasal doses of CBT101 in healthy male volunteers and explored neurophysiological evidence of central pharmacodynamic activity using quantitative EEG (qEEG) and event-related potentials (ERPs). Methods: This was a randomized, double-blind, single-center, placebo-controlled phase 1 trial including single ascending dose (SAD) and multiple ascending dose (MAD) parts. Forty-eight healthy male volunteers were randomized 3:1 to CBT101 or placebo. CBT101 was administered intranasally at 4.2, 8.4, or 12.6 mg in the SAD part and at 4.2, 8.4, or 12.6 mg/day for 14 days in the MAD part. The primary objective was safety and tolerability. Secondary analyses assessed quantitative EEG (qEEG) and event-related potentials (ERPs) as pharmacodynamic evaluations. Results: No serious or severe treatment-emergent adverse events occurred, no dose-limiting toxicity was observed, and no clinically relevant safety findings were reported. As expected, plasma CBT101 concentrations were below the limit of quantification in all analyzed samples. qEEG analyses identified an acute post-dose increase in relative beta activity after single dosing. After repeated dosing, the qEEG profile evolved toward a more sustained pattern characterized by beta-1 modulation and early gamma-band changes. ERP/P300 analyses showed a transient decrease in P300 latency, with no statistically significant change in P300 amplitude. Conclusion: Intranasal CBT101 was safe and well tolerated across the evaluated SAD and MAD dose ranges in healthy male volunteers. Convergent qEEG and ERP findings provided early neurophysiological evidence of central pharmacodynamic engagement. These findings support continued clinical development of CBT101 for disorders associated with impaired neuronal energy homeostasis. Clinical trial registration: ClinicalTrials.gov, identifier: NCT07050316.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2026.1940627