Evaluation of the Safety and Efficacy of N-desmethylclobazam in Patients With Peripheral Neuropathic Pain (NDMC-201)

May 8, 2023 updated by: Besson Marie

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
76

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Switzerland
    • GE
      • Geneva, GE, Switzerland, 1205
        • Geneva University Hospitals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Informed Consent as documented by signature (Appendix 1: Informed Consent Form);
  • Male or female participants (if female: post-menopausal or surgically sterile, or using a highly effective method of contraception);
  • Between 18 and 85 years of age;
  • Body mass index ≥ 18 and < 40 (kg/m2);
  • Patients diagnosed with small fiber neuropathy OR suffering from peripheral neuropathic pain related to diabetic peripheral neuropathy; post-herpetic neuralgia; HIV-associated neuropathic pain; post-traumatic/postoperative peripheral neuropathy; chemotherapy associated peripheral neuropathy or nerve root/medullar compression with sensory/motor deficit OR presenting with neuropathic pain associated with diagnosed rare hereditary or acquired neurological disease; AND who presented insufficient response to at least one attempt with one of the currently recommended pharmacological treatment for neuropathic pain taken at efficacious dose OR who have interrupted treatment because of tolerance issue OR who have previously declined pharmacological pain management;;
  • Pain duration for at least 3 months;
  • Preceding week pain recall score ≥ 4 on NRS Scale;
  • Score ≥ 4 on DN4 questionnaire;
  • Willing to withdraw from prohibited medications;
  • Poor-metabolizers (PM) for CYP2C19 are only eligible for Sequence 3

Exclusion Criteria:

  • Contraindications to benzodiazepines.(including known hypersensitivity reaction)
  • Women who are pregnant or breast feeding or who intend on becoming pregnant during the course of the study;
  • Woman of childbearing potential, not using and not willing to continue using a highly effective method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases;
  • Abnormal ASAT or ALAT plasma levels (> 3x ULN);
  • Reduced renal function (GFR < 60 mL/min/1.73m2);
  • Changes in existing (or addition of new) concomitant interventional pain management (including local anaesthetic infiltration, local nerve block, central neurostimulation therapy) and other non-pharmacological intervention such as desensitization techniques, acupuncture, transcutaneous electrostimulation, hypnosis;
  • Co-existing nociceptive or inflammatory aetiology to the current pain symptoms;
  • Unable to withdraw from prohibited medications before randomization;
  • Epilepsy;
  • History of drug, alcohol or substance abuse in the past 5 years (with the exception of stable opioid substitution therapy in the past 5 years);
  • Current unstable psychiatric disorder or any such disorder that may impair patient's abilities to follow study procedures;
  • Sleep apnea (unless treated with CPAP with an oxygen desaturation index < 5 per hour), myasthenia gravis, severe respiratory failure;
  • Participation in another study with investigational drug within the 3 month preceding and during the present study (a wash-out of period at least 3 months is necessary prior to screening).
  • Score < 24 on MMS in patients over 65 years of age

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NDMC 40 mg/day
Oral administration of two NDMC 20mg capsules per day over 6 weeks
Drug: NDMC
Repeated oral administration of ascending daily doses of NDMC (40mg, 60mg,120mg/day) vs placebo in 3 sequential cohorts
Other Names:
  • Placebo
Experimental: NDMC 60 mg/day
Oral administration of three NDMC 20mg capsules per day over 6 weeks
Drug: NDMC
Repeated oral administration of ascending daily doses of NDMC (40mg, 60mg,120mg/day) vs placebo in 3 sequential cohorts
Other Names:
  • Placebo
Experimental: NDMC 120 mg/day
Oral administration of six NDMC 20mg capsules per day over 6 weeks
Drug: NDMC
Repeated oral administration of ascending daily doses of NDMC (40mg, 60mg,120mg/day) vs placebo in 3 sequential cohorts
Other Names:
  • Placebo
Placebo Comparator: Placebo
Oral administration respectively, according to the experimental arm considered, of two, three or six placebo capsules per day over 6 weeks
Drug: NDMC
Repeated oral administration of ascending daily doses of NDMC (40mg, 60mg,120mg/day) vs placebo in 3 sequential cohorts
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Weekly Average of daily Pain intensity score (WAP)
Time Frame: Week 0, Week 6 following first drug administration
Participant will self-rate once every day his average daily pain. The weekly average of daily pain intensity score will be derived from the 7 (at least 5) recordings preceding Baseline (Week 0) and Final evaluation (Week 6). Numerical Rating Scale = 0 "no pain" to 10 = "worst possible pain". The primary outcome will be the change from Baseline to Final evaluation.
Week 0, Week 6 following first drug administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evolution of Weekly Average of daily Pain intensity score (EWAP)
Time Frame: Week 0, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 following first drug administration
Assessment of the evolution overtime of the weekly average of daily pain intensity score between Baseline (Week 0) and Final evaluation (Week 6).
Week 0, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 following first drug administration
Weekly Average of daily subjective feeling of Sedation (WAS)
Time Frame: Week 0, Week 6 following first drug administration
Participant will self-rate once every day his daily subjective feeling of sedation. The weekly average of daily subjective feeling of sedation score will be derived from the 7 (at least 5) recordings preceding Baseline (Week 0) and Final Evaluation (Week 6). Numerical Rating Scale = 0 "not sleepy" to 10 = "extremely sleepy".
Week 0, Week 6 following first drug administration
Evolution of Weekly Average of daily subjective feeling of Sedation (EWAS)
Time Frame: Week 0, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 following first drug administration
Assessments of the evolution overtime of the weekly average of daily subjective feeling of sedation score, each week between Baseline (Week 0) and Final evaluation (Week 6).
Week 0, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 following first drug administration
Composite 2-Dimension Score (C2-D)
Time Frame: Week 0, Week 6 following first drug administration
The Composite 2-Dimension score will assess the benefit/tolerance balance of NDMC for each dose. The score is defined as the aggregated value of the changes between baseline and final evaluation on the weekly average of daily pain intensity score and the weekly average of daily subjective sedation score. Score ranges from -10 to + 16. Score ≤ -2 indicates a favorable balance and score ≥ 2 an unfavorable balance.
Week 0, Week 6 following first drug administration
Evolution of Composite 2-Dimension Score (EC2-D)
Time Frame: Week 0, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 following first drug administration
Assessments of the evolution overtime of the Composite 2-Dimension score, each week between Baseline (Week 0) and Final evaluation (Week 6).
Week 0, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 following first drug administration
Douleur neuropathique 4 questionnaire (DN4)
Time Frame: Week 0, Week 2, Week 6 following first drug administration
Participant will complete the DN4 questionnaire which is a screening tool for neuropathic pain consisting of interview questions. This questionnaire gives a score ranging from 0 (better) to 10 (worse); a score ≥4 is an indicator of plausible neuropathic pain.
Week 0, Week 2, Week 6 following first drug administration
Neuropathic Pain Symptom Inventory (NPSI)
Time Frame: Week 0, Week 2, Week 6 following first drug administration
Participant will complete the NPSI questionnaire which is an inventory tool for neuropathic pain consisting of interview questions.This questionnaire has 12 scaled scores and gives a score ranging from 0 (better) to 100 (worse)
Week 0, Week 2, Week 6 following first drug administration
Short Form Questionnaire (SF-36)
Time Frame: Week 0, Week 2, Week 6 following first drug administration
Participant will complete the health status questionnaire consisting of 36 interview questions. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100. Lower scores = more disability, higher scores = less disability.
Week 0, Week 2, Week 6 following first drug administration
Hospital Anxiety and Depression Scale (HADS)
Time Frame: Week 0, Week 2, Week 6 following first drug administration
Participant will complete the anxiety and depression questionnaire consisting in two sets of 7 questions on anxiety or depression. HADS gives anxiety and depression scores both ranging from 0 (better) to 21 (worse)
Week 0, Week 2, Week 6 following first drug administration
Patient Global Impression of Change (PGIC)
Time Frame: Visit 1 to Visit 7
Participant will complete the PGIC questionnaire, which is a 7-point scale ranging from -3 (very much worse), 0 (no change), to +3 (very much improved) answering the question: "Please, indicate how you feel now, compared to how you felt before receiving treatment in this study"
Visit 1 to Visit 7
Clinician Global Impression of Improvement (CGI-I)
Time Frame: Week 0, Week 2, Week 6 following first drug administration
Investigator will complete CGI questionnaire which is a 7-point CGI scale: from 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) to 7 (very much worse) answering the question: "Please, indicate how much the patient's condition has improved or worsened relative to a baseline state at the beginning of the intervention"
Week 0, Week 2, Week 6 following first drug administration
Medical Outcome Study Sleep Score (MOS-Sleep)
Time Frame: Week 0, Week 2, Week 6 following first drug administration
Participant will complete the MOS-sleep questionnaire, which is composed of 12 items. Higher scores reflect more of the attribute implied by the scale names
Week 0, Week 2, Week 6 following first drug administration
Responder Rates (30% / 50%)
Time Frame: Week 0, Week 6 following first drug administration
Participants will be dichotomized into "responders" and "non-responders" categories. These transformations will be based on the reduction of at least 30%, respectively 50%, of the weekly average daily pain intensity score between Baseline (Week 0) and Final evaluation (Week 6).
Week 0, Week 6 following first drug administration
Rescue Medication Rate
Time Frame: Week 0, Week 6 following first drug administration
Participants will be dichotomized into "rescue med" and "no rescue med" categories. This transformation will be based on the use of rescue medications between Baseline (Week 0) and Final evaluation (Week 6).
Week 0, Week 6 following first drug administration
Withdrawal Rate
Time Frame: throughout the study (up to 6 weeks)
Participants will be dichotomized into "early withdrawal" and "completion" categories. This transformation will be based on the occurrence of premature withdrawal related to lack of efficacy or due treatment emergent adverse effect between Baseline (Week 0) and Final evaluation (Week 6).
throughout the study (up to 6 weeks)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Steady state NDMC Cmin concentration
Time Frame: Week 0, Week 2, Week 6 following first drug administration
Determination of mean NDMC Cmin concentrations at steady state following daily administration (40mg, 60mg, 120mg) in 3 sequential cohorts of patients.
Week 0, Week 2, Week 6 following first drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Besson Marie

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marie Besson, MD, University Hospital, Geneva

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 24, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 11, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 21, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 10, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2019-01113

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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