No registrations found.
ID
Source
Brief title
Health condition
ARID1B
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 (λz) with the respective half-life, t½
• 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
Secondary outcome
N.A.
Background summary
Clonazepam is a registered and safe drug which is being used for the treatment of epilepsy. Preclinical experiments show that clonazepam rescues some of the preclinical phenotypes in ARID1B +/- mice. There is currently no treatment for ARID1B-related intellectual disability. The aim of this study is to assess the efficacy and safety of clonazepam in patients with ARID1B-related intellectual disability.
Study objective
• clonazepam administration has acute beneficial effects compared
to placebo on neurocognitive tests.
• multiple-doses clonazepam has beneficial effects compared to placebo on behaviour and cognitive function in ARID1B patients as measured by the ABC, and CGI-I scale.
Study design
-28 Days till EOS
Intervention
Clonazepam and placebo
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
• Able to perform at least 5 of the 6 NeuroCart® activities.
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
Recruitment
IPD sharing statement
Plan description
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8792 |
| CCMO | NL71395.056.19 |
| OMON | NL-OMON52899 |