Safety, Tolerability, and Pharmacokinetic Profile of the Low‐Impact Ampakine CX1739 in Young Healthy Volunteers
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: AMPA‐type glutamate receptors (AMPARs) mediate the majority of fast excitatory synaptic transmission in the mammalian brain. Ampakines, positive allosteric modulators of AMPAR, hold significant potential for the treatment of a wide range of neurological/neuropsychiatric disorders in which excitatory synaptic transmission is compromised. Low‐impact ampakines are a distinct subset of ampakines that accelerate channel opening yet minimally affect receptor desensitization, which may explain their lack of seizurogenic effects at therapeutic doses in preclinical models. CX1739 is a low‐impact ampakine that has shown efficacy in preclinical studies. The current clinical study examined the tolerability and pharmacokinetics of CX1739 in healthy male volunteers in a 2‐part study. Part A was a single dose escalation study (100‐1200 mg, 48 patients) and Part B was a multiple dose ascending study (300‐600 mg BID for 7‐10 days, 32 patients). CX1739 was well tolerated up to 900 mg once daily (QD) and 450 mg twice a day, with the prominent side effects being headache and nausea. Importantly, the half‐life of CX1739 was 6‐9 hours, and T max was 1‐5 hours. CX1739 C max and AUC were dose‐proportional. These findings thus set the stage for further explorations of this drug candidate in phase 2 clinical studies.
DOI: 10.1002/cpdd.1475
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Funder: RespireRx Pharmaceuticals
OpenAlex ID: W4402678098