Insomnia in children and adolescents with autism, intellectual disability or ADHD MedDRA version: 20.0 Level: PT Classification code 10022443 Term: Insomnia related to another mental condition System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: trazodone hydroclorite
Product Code: 152PO17433
Pharmaceutical Form:
INN or Proposed INN: trazodone hidrocloride
CAS Number: 25332-39-2
Current Sponsor code: 152
Concentration unit: mg/
Sponsors
AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient provided a signed written informed consent (including personal data processing) by parents/legal guardian 2. Patient with documented assent by patient in accordance with age and maturity level, in line with 2017 ethical considerations for clinical trials on medicinal products conducted with minors 3. Patient is male or female, 2-17 years of age (inclusive) 4. Patient diagnosed with autism, intellectual disability or ADHD according to ICD-10 (F84.0, F90.9, F79) or DSM-5 (299.00, 314.01, 319) criteria 5. Patient diagnosed with insomnia according to ICSD-3 (American Academy of Sleep Medicine, 2014) criteria 6. Sleep disturbance scale for children with a total score > 60 7. Patient on a stable therapy for their primary neurodevelopmental disorders (NDDs), apart from medications specified in the ‘exclusion criteria’ 8. Patient taking any sleep-inducing medication has completed the required wash-out period of 7 days Are the trial subjects under 18? yes Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patient with ascertained or presumptive hypersensitivity to trazodone and/or its excipients 2. Patient with history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study 3. Patient treated with any form of trazodone within 2 weeks prior to the inclusion in the study 4. Patient not responding to previous trazodone-based therapy based on past medical history records in the last 2 years 5. Patient taking any medications (except those foreseen for their primary NDDs) that prolong the QT/corrected QT interval or included in the "Interactions with other medicinal products and other forms of interaction" of trazodone Summary of Product Characteristics within 2 weeks before the start of the study and during the study duration 6. Patient is female affected by Rett syndrome 7. Patient with a previous diagnosis of HIV, hepatitis B virus surface antigen or hepatitis C virus 8. For female patient: pregnancy or lactation 9. Patient is adolescent female of childbearing potential who is sexually active and unwilling or unable to use an highly effective birth control method, which includes combined ( estrogen and progestogen containing) – hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, sexual abstinence for at least 1 month prior to study entry, throughout the duration of the study and 1 month following study completion 10. Patient is adolescent female of childbearing potential who is sexually abstinent and does not agree to continue practicing abstinence or to use one of the highly effective birth control methods should her sexual activity commence 11.Patient is adolescent male who is sexually active and unwilling or unable to use a condom as contraception method throughout the duration of the study and 1 month following study completion 12. Patient is adolescent male who is sexually abstinent and does not agree to continue practicing abstinence or to use a condom as contraception method throughout the duration of the study and 1 month following study completion. 13. Patient with corrected QT interval using Fridericia´s formula (QTcF) value =440 msec for male and =450 msec for female, for all age groups 14. Patient with history of risk factors for torsade de pointes (e.g. heart failure, hypokalaemia, family history of long QT syndrome, cardiac arrhythmias, bradycardia, cardiac conduction abnormalities, cardiac hypertrophy, cardiomyopathy, chronic cardiac insufficiency) 15. Patient with evident history of drug and/or alcohol abuse in adolescents (12 to = 17 years of age) 16. Patient with physical abnormalities or clinically significant abnormal laboratory test results relevant for the study assessments or the patient’s safety 17. Patient with history of significant renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study 18. Patient with history of blood loss exceeding 3% of the patient’s total blood volume within 1 month before the study 19. Patient with any condition (surgical or medical) which will affect absorption, distribution, metabolism and/or excretion of the drug 20. Patient and parents/legal guardian, who are unable to comprehen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the PK of trazodone after single and repeated doses in patients aged from 2 to = 17 years;Secondary Objective: The secondary objectives of this study are: - to establish the pharmacokinetic-pharmacodynamics (PKPD) relationship of trazodone, as assessed by actigraph measures. - to evaluate the concentration-QT internal correlation. - to define the dose rationale in children and adolescents aged from 2 to = 17 years taking into account the therapeutic exposure range in adults. - to evaluate the safety and tolerability of trazodone in children and adolescents aged from 2 to = 17 years. - to assess palatability of trazodone.;Primary end point(s): Primary PK parameters for trazodone after single and repeated oral administration of trazodone will include apparent oral clearance (CL/F), apparent volume of distribution (Vd/F) and, absorption rate constant (Ka). Secondary parameters will be derived from model predicted profiles: AUC, Cmax, Cmin, Css, Ctrough, Tmax;Timepoint(s) of evaluation of this end point: V1(1st dose), V2 (4th dose) and V3(10th dose) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacodynamic Parameters: • Exploratory analysis of the data will include correlation between PK parameters (AUC, Css, Cmax) and clinical endpoints (sleep latency time and total sleeping time) as assessed by actigraphy • Exploratory analysis of concentration-QT interval correlation • If data allows, PKPD modelling will be applied to derive relevant parameters, such as potency and maximum effects on sleep latency and total sleep time from baseline levels Safety/Tolerability;Timepoint(s) of evaluation of this end point: In the course of the study | — |
Countries
Italy, Spain
Contacts
Public ContactValeria Tellone -Study Manager
Aziende Chimiche Riunite Angelini Francesco ACRAF S.p.a. (Angelini s.p.a.)
Outcome results
None listed