Evaluation of the Safety and Efficacy of N-desmethylclobazam in Patients With Peripheral Neuropathic Pain
Status:
Recruiting
Trial end date:
2021-07-31
Target enrollment:
Participant gender:
Summary
Neuropathic pain (NP) affects up to 8% of the general population and its successful
management is an unmet medical need. Half of the patients report inadequate response to
therapy and unwanted side effects such as sedation and cognitive impairments, limiting drug
use in daily practice and significantly accounting for the high incidence of treatment
failure. Dysfunction of synaptic inhibition within the spinal cord is known to be one of the
main contributing factors to central sensitization that governs NP. Facilitation of GABAergic
inhibition in the dorsal horn through GABAA receptors allosteric modulation would be a
rational approach to NP management. New insights on the associations between GABAA receptors
α subunits and function have opened new perspectives in preclinical research. Data from
genetically modified mice demonstrates the possibility, through selective allosteric
modulation of the GABAA receptor, to induce its beneficial antihyperalgesic effects without
inducing its cognitive and sedative effects. N-Desmethylclobazam (NDMC), clobazam's main
active metabolite, demonstrated in vitro and in vivo a high selectivity profile with a clear
preference for GABAA α2-subtypes receptors (antihyperalgesia) over α1 receptors responsible
for sedative effects across a wide concentration range. Taking into consideration the high
prevalence and burden of neuropathic and chronic pain worldwide and the fact that these
patients are nowadays left with sedative and only partially effective drugs, NDMC qualifies
as a good molecule to seek confirmation of the clinical utility of selective GABAA allosteric
modulators in NP patients.The main objective is to assess the efficacy of repeated doses of
NDMC on neuropathic pain compared to placebo.