Evidence map›Paper›PMID 42886059›Full record

Trial reportEuropean journal of pain (London, England)2026

The α2-Subunit Preferring GABA Positive Allosteric Modulator, N-Desmethyl-Clobazam in Peripheral Neuropathic Pain Patients: Results of a Phase IIa Randomised Placebo-Controlled Ascending Dose Study.

M Besson, A Matthey, Y Daali, A Ramsahye, C Samer, J Desmeules, F Curtin

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase II
PubMed Publisher
In one paragraph

Trial report in European journal of pain (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03375034 (Exploring the Role of the GABAergic Modulation in Pain Transmission in Human. Effects of the GABAA Agonist N-desmethylclobazam on Central Sensitization), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03375034 phase1completednot on this map

Exploring the Role of the GABAergic Modulation in Pain Transmission in Human. Effects of the GABAA Agonist N-desmethylclobazam on Central Sensitization: a Pharmacodynamic and Pharmacokinetic Study in Healthy Volunteers

TypeinterventionalSponsorJules DesmeulesRan2017 to 2018Enrolled56ConditionsNeuropathic PainArmsNDMC 20mg, NDMC60mg, Clonazepam 1.5mg, Placebo
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

M BessonDivision of Clinical Pharmacology and Toxicology, Department of Acute Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
A MattheyDivision of Clinical Pharmacology and Toxicology, Department of Acute Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
Y DaaliDivision of Clinical Pharmacology and Toxicology, Department of Acute Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
A RamsahyeDivision of Clinical Pharmacology and Toxicology, Department of Acute Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
C SamerDivision of Clinical Pharmacology and Toxicology, Department of Acute Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
J DesmeulesDepartment of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
F CurtinDivision of Clinical Pharmacology and Toxicology, Department of Acute Care Medicine, Geneva University Hospitals, Geneva, Switzerland.

Funding

Swiss innovation agency (Innosuisse) 37848.1 IP-LS
6 · The paper itself

Abstract

backgroundN-desmethyl clobazam (NDMC), an α2-preferring-α1-sparing-GABA

methodRandomised, ascending doses, double-blind, placebo-controlled study, evaluating 40, 60, 120 mg of NDMC. Primary outcome was the change in weekly average daily pain (WADP) on a Numerical Rating Scale (NRS) from baseline (V1) to the end of the study (V7). Secondary outcomes included sedation (subjective NRS), quality of life (SF36), global and patient impression of change (CGI, PCGI). PK and safety data were collected. The study was prematurely terminated due to recruitment challenges related to the COVID-19 pandemic.

resultsThirty-three out of the planned 76 patients were enrolled. The mean reduction in WADP from V1 to V7 was -1.53 points for placebo and -1.99 across all NDMC doses (delta = 0.46, p = 0.47). When analysed according to NDMC plasma concentrations, the mean WADP reduction was 1.53 (SD 1.58) for placebo 1.78 (SD 1.79) for NDMC < 1000 ng/mL, and 2.40 (SD 1.46) for NDMC ≥ 1000 ng/mL. The prevalence of 30% pain reduction was 38.5% (placebo) and 83.3% (NDMC ≥ 1000 ng/mL). Logistic regression analysis indicated that NDMC ≥ 1000 ng/nL was predictive of a 30% pain reduction (odds ratio = 12.5, p = 0.04). NDMC was well tolerated.

conclusionDespite being underpowered, this study revealed a consistent exposure-response relationship along with a favourable safety profile for NDMC in patients with NP.

trial registrationClinicalTrial.gov (NCT03375034); kofam.ch (SNCTP000003517). SIGNIFICANCE STATEMENT: This work presenting the Phase II data of the new antihyperalgesic compound, N-Desmethyl-Clobazam (NDMC) in peripheral neuropathic pain patients support further investigation into the role in modulating GABAergic pathways as a potential therapeutic target for neuropathic pain. This objective is particularly relevant given the limited efficacy of standard pharmacological treatments for neuropathic pain, which often requires a multimodal approach targeting the multiple pathways involved in pain pathophysiology.

Indexed as

AnalgesicsClobazamNeuralgiaAdultAgedDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansMaleMiddle AgedPain MeasurementQuality of LifeTreatment OutcomeAnalgesicsClobazam

Identifiers

PMID42886059

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.