NCT04480164

Evaluation of the Safety and Efficacy of N-desmethylclobazam in Patients With Peripheral Neuropathic Pain

A Randomized Double-blind Ascending-dose Placebo-controlled Study of N-desmethylclobazam in Patients With Peripheral Neuropathic Pain

• Status: Suspended
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 76 (estimated)
• Sponsor: Besson Marie · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Neuropathic Pain

Interventions

Type	Name	Description
DRUG	NDMC	Repeated oral administration of ascending daily doses of NDMC (40mg, 60mg,120mg/day) vs placebo in 3 sequential cohorts

Timeline

• Start date: 2020-06-24
• Primary completion: 2022-09-01
• Completion: 2023-05-31
• First posted: 2020-07-21
• Last updated: 2023-05-10

Locations

1 site across 1 country: Switzerland