E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Abnormal or excessive body fat accumulation/excess proportion of total body fat |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029883 |
E.1.2 | Term | Obesity |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
To assess the safety and tolerability of liraglutide at doses up to 3.0 mg in an obese adolescent population aged 12-17 years and Tanner stage 2-5 |
|
E.2.2 | Secondary objectives of the trial |
To assess the pharmacokinetics (PK) of liraglutide at doses up to 3.0 mg in an obese adolescent population aged 12-17 years and Tanner stage 2-5 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female subjects aged 12-17 years (both inclusive) at time of randomisation with Tanner stage 2-5 pubertal development
- BMI corresponding to ≥ 30 kg/m^2 for adults by international cut-off points and ≤ 45 kg/m^2 and ≥ 95th percentile for age and gender
- Fasting plasma glucose < 7.0 mmol/L (126 mg/dL) (central laboratory analysis) |
|
E.4 | Principal exclusion criteria |
- Subjects with clinically diagnosed secondary causes of childhood obesity such as chromosomal abnormalities (e.g. Turner syndrome), syndromic obesity (e.g. Prader Willi syndrome) or endocrinologic disorders (e.g. Cushing Syndrome)
- Subjects with confirmed diagnosis of bulimia
- Subjects with Tanner stage 1 development (prepubertal)
- Diagnosis of type 1 or type 2 diabetes mellitus as judged by the investigator
- Previous treatment with a GLP-1 receptor agonists (e.g. exenatide or liraglutide or other), DPP-4 inhibitors, orlistat or other weight lowering medication, any antipsychotic medication or systemic corticosteroids within the last 3 months
- Currently using or have used within 3 months before screening for this trial: any systemic treatment that in the opinion of the investigator interferes with PK, PD and safety endpoints
- Surgical treatment for obesity
- Past or current chronic or idiopathic pancreatitis, or any of the following:
o amylase or lipase > 2 times UNR
o triglycerides > 500 mg/dL
o calcium > UNR
o history of gallstones (not treated by cholecystectomy)
- Uncontrolled treated or untreated hypertension >99th percentile for age and gender in children
- History of major depressive disorder or history of other severe psychiatric disorders (e.g. schizophrenia or bipolar disorder) that could in the opinion of the investigator interfere with trial compliance or subject safety
- Subjects with a history of suicide attempts or history of any suicidal behaviour within the past month before entry into the trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of treatment emergent adverse events (TEAEs) recorded |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From the time of first dosing and until completion of follow-up visit (up to 6 weeks treatment and 5-14 days subsequent follow-up period) |
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E.5.2 | Secondary end point(s) |
Safety:
Incidence of liraglutide antibody
Pharmacokinetics:
1 - At steady state at each dose step: Ctrough
2 - At steady-state : model-derived AUCĪ, t½, CL/F, V/F |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety:
At follow-up (up to 6 weeks treatment and 5-14 days subsequent follow-up period)
Pharmacokinetics:
1 - After 7, 14, 21, 28 and 35 days of treatment
2 - Last dose day, after up to 6 weeks treatment |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Safety and tolerability in adolescents |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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
|
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | 18 |