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Peer-reviewedCC BY 4.0Frontiers in Neurology

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

  • Henri Benech1
  • Lila Krebs-Drouot2
  • Geoffrey Viardot3
  • Valérie Bertaina-Anglade3
  • Clara Lhotellier1
  • Victoria Flament1
  • Camille Roucairol1
  • Aloïse Mabondzo4
  • Jean-Louis Pinquier5
  • Thomas Joudinaud1
5 affiliations
  1. 1Ceres-Brain Therapeutics, ICM, Hôpital Pitié-Salpêtrière
  2. 2Eurofins Optimed
  3. 3Biotrial Neuroscience
  4. 4Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé, SPI/LENIT
  5. 5Decisions R&D consulting
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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.

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Cite

BibTeXRIS
BibTeX
@article{benech2026intranasal,
  title = {{Intranasal CBT101 demonstrates favorable safety and neurophysiological evidence of central activity in healthy male volunteers}},
  author = {Henri Benech and Lila Krebs-Drouot and Geoffrey Viardot and Valérie Bertaina-Anglade and Clara Lhotellier and Victoria Flament and Camille Roucairol and Aloïse Mabondzo and Jean-Louis Pinquier and Thomas Joudinaud},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1940627},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1940627/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Intranasal CBT101 demonstrates favorable safety and neurophysiological evidence of central activity in healthy male volunteers
AU  - Henri Benech
AU  - Lila Krebs-Drouot
AU  - Geoffrey Viardot
AU  - Valérie Bertaina-Anglade
AU  - Clara Lhotellier
AU  - Victoria Flament
AU  - Camille Roucairol
AU  - Aloïse Mabondzo
AU  - Jean-Louis Pinquier
AU  - Thomas Joudinaud
PY  - 2026
DA  - 2026/10/22
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1940627
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1940627/full
AB  - 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.
SN  - 1664-2295
ER  -