Neuropathic PainPhase 1NDMC-101NCT03375034
Exploring the Role of the GABAergic Modulation in Pain Transmission in Human
A Phase 1 study testing NDMC 20mg, NDMC60mg and Clonazepam 1.5mg in people with Neuropathic Pain, run by Jules Desmeules at 1 site in Switzerland.
Trial summary
Neuropathic pain affects about 7% of the general population in European countries. Meta-analyses indicate that only a minority of neuropathic pain patients has adequate response to drug therapy and management of neuropathic pain is still an unmet medical need. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Neuropathic Pain
- What is being tested?
- NDMC 20mg, NDMC60mg and Clonazepam 1.5mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteSwitzerland
- Study dates
- 30 Mar 2017to 31 Jan 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male subject, age between 18 and 50 years old
- Caucasian
- Type 3 skin phototype (white skin that can tan gradually and burns moderately)
- Non smoker or moderate smoker (< 10 cigarettes/day)
- No clinically abnormal findings on history and/or on physical examination
- Positive minimal erythema dose (MED) determination
Who cannot join
- Any active significant illness
- Current or past history of drug and alcohol abuse or current intake of more than 3 glasses of alcohol a day or more than 21 glasses of alcohol per week
- Psychotropic drug intake during the last month
- Sun allergy or any skin disease
- Any regular drug intake
- CYP2C19 poor metabolizer (phenotype)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Neuropathic pain affects about 7% of the general population in European countries. Meta-analyses indicate that only a minority of neuropathic pain patients has adequate response to drug therapy and management of neuropathic pain is still an unmet medical need. New insights into the contribution of defined subtypes of GABAA receptors (GABAARs) to the different clinical effects of benzodiazepines, including analgesia, have suggested that α1-sparing selective benzodiazepines, such as N-desmethylclobazam (NDMC), may be a new realistic alternative for the treatment of neuropathic pain. Results from our previous study in healthy volunteers assessing the antihyperalgesic and sedative effects of benzodiazepines on a UVB-induced pain model of central sensitization showed that, at the time of maximum effect, clobazam and clonazepam antihyperalgesic effect was greater than placebo by respectively 15.7% (95% CI 0.8 - 30.5) and 28.6% (95% CI 4.5 - 52.6), p<0.05. Moreover difference in sedation (VAS), as compared to placebo, was only significant for clonazepam 26.3mm (95%CI 15.0-37.7), p<0.001. Our preclinical data also demonstrate that, in recombinant receptors, NDMC has a better α2- over α1GABAARs activity ratio than clobazam and diazepam. And, unlike diazepam, NDMC caused no or modest sedation at antihyperalgesic doses in two strains of wild-type mice. In addition NDMC α2/α1 in vitro activity profile and long term clinical experience from its marketed parent compound (clobazam) make it an advisable clinical candidate for further proof-of-concept assessments in human. Therefore the Geneva University Hospitals have manufactured a new chemical entity and initiated a drug development program for NDMC starting with this proof-of-concept phase 1b randomized double-blind crossover (4 arms) study that will assess the analgesic and sedative effects of NDMC 20mg and 60mg compared to clonazepam 1.5 mg or placebo on a UVB-induced erythema pain model in healthy volunteers.
- Conditions
- Neuropathic Pain
- Being tested
- NDMC 20mg, NDMC60mg, Clonazepam 1.5mg, Placebo
- Keywords
- Chronic pain, Benzodiazepine, Central sensitization, Selective compound, GABAA receptors, Antihyperalgesia, RCT
- Medical subject headings
- Neuralgia, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NDMC 20mgDrug
Oral administration of one NDMC 20mg capsule and two Placebo capsules
NDMC60mgDrug
Oral administration of three NDMC 20mg capsules
Clonazepam 1.5mgDrug
Oral administration of three clonazepam 0.5mg capsules
PlaceboDrug
Oral administration of three Placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| NDMC 20mg | Experimental | oral single dose Receives: Drug: NDMC 20mg |
| NDMC 60mg | Experimental | oral single dose Receives: Drug: NDMC60mg |
| Clonazepam 1.5mg | Active comparator | oral single dose Receives: Drug: Clonazepam 1.5mg |
| Placebo | Placebo comparator | oral single dose Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the area of secondary hyperalgesia from baseline
The mapping of the area of secondary hyperalgesia is determined by pricking the skin surrounding the erythema with a hand-held von Frey filament (235 mN), normally felt as non-painful.
The punctuated probe is moved along the 8 radial lines defined by the center (erythema) and the corners of a regular octagon. Testing starts outside the hyperalgesic area and the probe is moved towards the center in steps of 5 mm. The position is marked where the pin-prick sensation changes to become painful. Once complete boundaries had been defined, the areas are transcribed onto clear film and weighed. The surface area will then be calculated based on a standard measure of the weight of an area of 100cm2.
Measured: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
Secondary outcomes (6)
Change in static mechanical pain threshold (SMPT) from baseline
Increasing pressure will be manually delivered at a constant rate of 10 g / sec with a von Frey electronic device (Bioseb, Id-Tech Bioseb, Chaville, France). SMPT is defined as the lowest pressure that produces a sensation of pain. This threshold will be determined at DAY1 before UVB exposition and at DAY2 on the primary area of hyperalgesia prior to the administration of the study drug to document hyperalgesia/allodynia.
Measured: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
Change in dynamic mechanical sensory VAS (DMSV) from baseline
Dynamic mechanical sensory is a good correlate of central sensitization and will be determined by gently stroking a hand-held cotton wool tip on the skin at a rate of approximately 1 cm/sec. Following a series of 10 strokes, the subject will be asked to score the intensity of the tactile sensation he experienced on a visual analogue scale (VAS; 0-100mm). This parameter will be determined at DAY1 before UVB exposition to document the integrity of the nociceptive fibres and at DAY2 on the primary area of hyperalgesia prior to the administration of the study drug to document hyperalgesia/allodynia.
Measured: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
Change in subjective feeling of sedation from baseline
The subjective degree of sedation will be evaluated on a Visual Analog Scale (VAS). The subject is asked to rate on a 100 mm scale (0=not at all and100 extremely) his level of drowsiness: "How sleepy do you feel now?"
Measured: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
Change in memory test score from baseline
Short term anterograde memory will be tested by memorizing a list of 20 words and 30 minutes later retrieve as many of them as possible.
Measured: Hour 4 and Hour 10 following drug administration
Change in AUC of N-desmethylclobazam from Baseline following administration of single dose (20mg, 40mg and 60mg) of N-desmethylclobazam
Venous blood sample will be collected to assess N-desmethylclobazam basic pharmacokinetic parameters following single dose administration
Measured: Hour 0.5, Hour 1, Hour 2, Hour 4, Hour 6, Hour 8, Hour 10, Hour 12, Hour 24, Hour 32, DAY 3, DAY 4, DAY 5, DAY 6, DAY 7, DAY 8, DAY 9, DAY 10, DAY 14 following drug administration
Change in AUC of N-desmethylclobazam from Baseline following administration of repeated doses (20mg) of N-desmethylclobazam
Venous blood sample will be collected to assess N-desmethylclobazam basic pharmacokinetic parameters following the administration of repeated doses of N-desmethylclobazam 20mg over 14 days
Measured: Hour 0.5, Hour 1, Hour 2, Hour 4, Hour 6, Hour 8, Hour 10, Hour 12, Hour 24 following drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2017
- Study start30 Mar 2017
- Primary completion28 Dec 2017
- Study completion31 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuropathic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jules Desmeules
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jules Desmeules, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03375034
- Sponsor's protocol ID
- PB_2016-02140
- Acronym
- NDMC-101
- Status last verified
- Apr 2019
- First submitted
- 8 Sep 2017
- Last updated
- 19 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Besson M, Matthey A, Daali Y, Ramsahye A, Samer C, Desmeules J, Curtin F. The alpha2-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. Eur J Pain. 2026 Oct;30(9):e70413. doi: 10.1002/ejp.70413.
PubMed 42886059
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03375034
- Acronym / sponsor ID
- NDMC-101 / PB_2016-02140
- Conditions
- Neuropathic Pain
- Keywords
- Chronic pain, Benzodiazepine, Central sensitization, Selective compound, GABAA receptors, Antihyperalgesia, RCT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Jules DesmeulesUniversity, hospital or other
- Study start
- 30 Mar 2017 (actual)
- Primary completion
- 28 Dec 2017 (actual)
- Study completion
- 31 Jan 2018 (actual)
- First posted
- 15 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neuropathic pain affects about 7% of the general population in European countries. Meta-analyses indicate that only a minority of neuropathic pain patients has adequate response to drug therapy and management of neuropathic pain is still an unmet medical need. New insights into the contribution of defined subtypes of GABAA receptors (GABAARs) to the different clinical effects of benzodiazepines, including analgesia, have suggested that α1-sparing selective benzodiazepines, such as N-desmethylclobazam (NDMC), may be a new realistic alternative for the treatment of neuropathic pain. Results from our previous study in healthy volunteers assessing the antihyperalgesic and sedative effects of benzodiazepines on a UVB-induced pain model of central sensitization showed that, at the time of maximum effect, clobazam and clonazepam antihyperalgesic effect was greater than placebo by respectively 15.7% (95% CI 0.8 - 30.5) and 28.6% (95% CI 4.5 - 52.6), p<0.05. Moreover difference in sedation (VAS), as compared to placebo, was only significant for clonazepam 26.3mm (95%CI 15.0-37.7), p<0.001. Our preclinical data also demonstrate that, in recombinant receptors, NDMC has a better α2- over α1GABAARs activity ratio than clobazam and diazepam. And, unlike diazepam, NDMC caused no or modest sedation at antihyperalgesic doses in two strains of wild-type mice. In addition NDMC α2/α1 in vitro activity profile and long term clinical experience from its marketed parent compound (clobazam) make it an advisable clinical candidate for further proof-of-concept assessments in human. Therefore the Geneva University Hospitals have manufactured a new chemical entity and initiated a drug development program for NDMC starting with this proof-of-concept phase 1b randomized double-blind crossover (4 arms) study that will assess the analgesic and sedative effects of NDMC 20mg and 60mg compared to clonazepam 1.5 mg or placebo on a UVB-induced erythema pain model in healthy volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NDMC 20mg | Experimental | Drug: NDMC 20mgoral single dose |
| NDMC 60mg | Experimental | Drug: NDMC60mgoral single dose |
| Clonazepam 1.5mg | Active comparator | Drug: Clonazepam 1.5mgoral single dose |
| Placebo | Placebo comparator | Drug: Placebooral single dose |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male subject, age between 18 and 50 years old
- Caucasian
- Type 3 skin phototype (white skin that can tan gradually and burns moderately)
- Non smoker or moderate smoker (< 10 cigarettes/day)
- No clinically abnormal findings on history and/or on physical examination
Key exclusion criteria (6 listed)
- Any active significant illness
- Current or past history of drug and alcohol abuse or current intake of more than 3 glasses of alcohol a day or more than 21 glasses of alcohol per week
- Psychotropic drug intake during the last month
- Sun allergy or any skin disease
- Any regular drug intake
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NDMC 20mgOral administration of one NDMC 20mg capsule and two Placebo capsules | Drug | NDMC 20mg |
| NDMC60mgOral administration of three NDMC 20mg capsules | Drug | NDMC 60mg |
| Clonazepam 1.5mgOral administration of three clonazepam 0.5mg capsules | Drug | Clonazepam 1.5mg |
| PlaceboOral administration of three Placebo capsules | Drug | Placebo |
Primary outcome
Change in the area of secondary hyperalgesia from baseline
Time frame: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
The mapping of the area of secondary hyperalgesia is determined by pricking the skin surrounding the erythema with a hand-held von Frey filament (235 mN), normally felt as non-painful. The punctuated probe is moved along the 8 radial lines defined by the center (erythema) and the corners of a regular octagon. Testing starts outside the hyperalgesic area and the probe is moved towards the center in steps of 5 mm. The position is marked where the pin-prick sensation changes to become painful. Once complete boundaries had been defined, the areas are transcribed onto clear film and weighed. The surface area will then be calculated based on a standard measure of the weight of an area of 100cm2.
6 secondary outcomes
Change in static mechanical pain threshold (SMPT) from baseline
Time frame: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
Change in dynamic mechanical sensory VAS (DMSV) from baseline
Time frame: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
Change in subjective feeling of sedation from baseline
Time frame: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
Change in memory test score from baseline
Time frame: Hour 4 and Hour 10 following drug administration
Change in AUC of N-desmethylclobazam from Baseline following administration of single dose (20mg, 40mg and 60mg) of N-desmethylclobazam
Time frame: Hour 0.5, Hour 1, Hour 2, Hour 4, Hour 6, Hour 8, Hour 10, Hour 12, Hour 24, Hour 32, DAY 3, DAY 4, DAY 5, DAY 6, DAY 7, DAY 8, DAY 9, DAY 10, DAY 14 following drug administration
Change in AUC of N-desmethylclobazam from Baseline following administration of repeated doses (20mg) of N-desmethylclobazam
Time frame: Hour 0.5, Hour 1, Hour 2, Hour 4, Hour 6, Hour 8, Hour 10, Hour 12, Hour 24 following drug administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2019.
- Derived from this study: PubMed 42886059Besson M, Matthey A, Daali Y, Ramsahye A, Samer C, Desmeules J, Curtin F. The alpha2-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. Eur J Pain. 2026 Oct;30(9):e70413. doi: 10.1002/ejp.70413.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NDMC 20mg, NDMC60mg and Clonazepam 1.5mg in people with Neuropathic Pain, run by Jules Desmeules at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the area of secondary hyperalgesia from baseline (time frame: Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03375034, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2019.