- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03375034
Exploring the Role of the GABAergic Modulation in Pain Transmission in Human (NDMC-101)
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Geneva, Switzerland, 1211
- UGeneva
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: NDMC 20mg
oral single dose
|
Oral administration of one NDMC 20mg capsule and two Placebo capsules
|
EXPERIMENTAL: NDMC 60mg
oral single dose
|
Oral administration of three NDMC 20mg capsules
|
ACTIVE_COMPARATOR: Clonazepam 1.5mg
oral single dose
|
Oral administration of three clonazepam 0.5mg capsules
|
PLACEBO_COMPARATOR: Placebo
oral single dose
|
Oral administration of three Placebo capsules
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10 following drug administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
|
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
|
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.
|
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
|
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?"
|
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
|
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.
|
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
|
Venous blood sample will be collected to assess N-desmethylclobazam basic pharmacokinetic parameters following single dose administration
|
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
|
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
|
Hour 0.5, Hour 1, Hour 2, Hour 4, Hour 6, Hour 8, Hour 10, Hour 12, Hour 24 following drug administration
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PB_2016-02140
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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