E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy children and adolescents |
Raske børn og unge |
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E.1.1.1 | Medical condition in easily understood language |
Healthy children and adolescents |
Raske børn og unge |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10022891 |
E.1.2 | Term | Investigations |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study aims to examine the pharmacokinetics of melatonin in different dosages in a broad paediatric age group to optimize treatment. Participants are given regular release melatonin 1,3 and 5 mg.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: Adverse events Tolerability evaluated by the modified Wong Baker scale Genetic variance in CYP1A2 The effect of puberty on melatonin metabolism
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Healthy subjects aged 3-17 years of age (both inclusive) who are able to swallow tablets of 9.5 mm 2. Signed informed consent form |
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E.4 | Principal exclusion criteria |
1. Diagnosis of a neurodevelopmental disorder 2. Participation in other studies that may interfere with results 3. If the investigator finds that the child is not eligible due to other diseases, cannot co-operate etc. 4. Hereditary fructose intolerance 5. Intake of medications that may interfere with the results i.e. Fluvoxamine, psoralenes, cimetidine, estrogens, quinolones, rifampicin, carbamezapine. 6. Unable to avoid caffeine, alcohol or nicotine 24 hours prior to study 7. Pregnancy (Pregnancy tests will be performed in girls from 12 years of age with menarche) 8. BMI for age outside the limits of ± 2SD (15) 9. Dental work in the last 24 hours
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the pharmacokinetic parameters Cmax, relative bioavailability of oral melatonin (Frel), AUC0-inf, AUC0-t, CL/F, t½, and tmax in salivary samples of healthy children and adolescents after single doses. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At each of the 4 visits 7 saliva samples will be obtained in one of two sampling groups. A: Baseline, 15 min, 40 min, 60 min, 120 min, 240 min and 360 min B: Baseline, 30 min, 50 min, 75 min, 180 min, 300 min, 420 min |
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E.5.2 | Secondary end point(s) |
Secondary outcomes 1. Adverse events registration 2. DLMO melatonin concentrations 3. Acceptability 4. Genotyping for CYP1A2 *1F alleles 5. Pharmacokinetic parameters compared between pre-pubertal and pubertal children
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Adverse events and Acceptability are assessed at all visits. Genotyping, DLMO and Tanner score (puberty) are assessed at visit 1 only. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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When 36 participants have completed all 3 trial days. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |