ARID1B syndrome ARID1B-related intellectual disability
Conditions
Interventions
Clonazepam and placebo
Sponsors
Centre for Human Drug Research
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: Part A, correlation blood-saliva PK. * Healthy male or female volunteers aged 18-30 years * Informed consent provided by volunteer Part B: ARID1B patients. * Informed consent provided by both parents, or the legal guardian prior to any study mandated procedure. * Known mutation in ARID1B * Assent provided by the participant. * Aged 6 years or older
Exclusion criteria
Exclusion criteria: Part A, healthy volunteers * Disorder that could interfere with saliva production. * Known hypersensitivity to clonazepam, other benzodiazepines or other excipients of the study medication. * Treatment with another investigational drug within 3 months prior to screening or more than 4 times a year. * History or clinical evidence of any disease and/or existence of a surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug. * History of severe respiratory problems or severe liver- or renal insufficiency. * Other medical or psychosocial history making the participant unsuitable for participation as determined by the treating paediatrician. * History or clinical evidence of alcoholism within the 3-year period prior to screening (i.e. regular use of more than 21 units of alcohol/week). * Clinically significant findings on physical examination. * Medications with a strong influence on CYP3A4 metabolism * Clinically meaningful blood loss (including blood donation), or a transfusion of any blood product within 12 weeks before screening. * Subjects with a BMI > 30 and/or cardiovascular, respiratory or immune system disorders Part B: ARID1B patients. * Clear indication of not wanting to participate during the study * Use of benzodiazepines or any other medication or drug with the potential to influence study related endpoints in the investigator*s opinion (including e.g. CYP3A4-related drugs). * Known hypersensitivity to clonazepam, other benzodiazepines or other excipients of the study medication. * History of severe respiratory problems or severe liver- or renal insufficiency. * Other medical or psychosocial history making the participant unsuitable for participation as determined by the treating paediatrician.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic endpoints Part A: serum and saliva. Part B: saliva only. * The maximum serum concentration, Cmax * The time to reach maximum serum concentration, tmax * The terminal disposition rate constant (*z) with the respective half-life, t* * The area under the serum concentration-time curve from zero to infinity, AUC0-inf * The area under the serum concentration-time curve from zero to t of the last measured concentration above the limit of quantification, AUC0-last * Clearance, Cl * Volume of distribution, Vz Trial@home endpoints * Physical activity * Sleep (duration, %light sleep, amount of times woken up) * Heart rate * Daily symptom scores * Tapping frequency, adaptive tracking, animal fluency (twice-weekly) Pharmacodynamic endpoints * NeuroCart o Adaptive Tracking o Animal fluency test o Body Sway o Saccadic Eye Movements o Smooth Pursuit Eye Movements o Tapping frequency * Questionnaires o ABC questionnaire (parents, teacher) o Clinician*s Global Impression of improvement (CGI-I) Tolerability / safety endpoints * Adverse events * Vital signs measurements * General physical examination findings | — |
Countries
Netherlands
Outcome results
None listed