E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
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 compare the change from baseline to the 6 months visit at the end of treatment, between
lifestyle intervention + exenatide 2 mg once weekly and lifestyle intervention + placebo,
in BMI SDS (according to WHO) for adolescents with obesity.
|
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate safety and tolerability.
2. To compare changes in beta-cell function within the groups and between the groups from baseline to the 6 months visit.
3. To compare changes in glucagon levels within the groups and between the groups from baseline to the 6 months visit.
4. To compare changes in cardiovascular risk factors and pattern changes in Free Fatty Acids (FFAs) within the groups and between the groups from baseline to the 6 months visit.
5. To compare changes in high sensitivity C-Reactive Protein (hs-CRP) within the groups and between the groups from baseline to the 6 months visit.
6. To compare changes in body composition characteristics within the groups and between the groups from baseline to the 6 months visit.
7. To compare changes in anthropometrics within the groups and between the groups from baseline to the 6 months visit.
8. To compare the change in s-BMI within the groups and between the groups from baseline to the 6 months visit. 9-11 in csp.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any study-specific procedures.
2. Males or females of age 10-18 years and 7 months.
3. Obesity (BMI SDS > 2.0 or age-adapted BMI > 30 kg/m2), according to WHO.
4. Not sexually active or usage of adequate anticonception. Female subjects must also have negative pregnancy tests.
Methods that can achieve a failure rate of less than 1% per year (Pearl index <1), when used consistently and correctly, are considered as highly effective birth control methods. Such methods include:
• Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
o oral
o intravaginal
o transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
o oral
o injectable
o implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomised partner
• Sexual abstinence (if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the preferred and usual lifestyle of the subject).
5. Ability to understand and comply with the requirements of the study
|
|
E.4 | Principal exclusion criteria |
1. Known syndromal obesity, such as Prader-Willi syndrome, Laurence-Moon syndrome or Bardet-Biedl syndrome.
2. Pregnancy or lactation.
3. Indigestion-causing diseases.
4. Severe gastrointestinal disease.
5. Total or partial gastric or small intestine resection.
6. Type 1 or Type 2 diabetes mellitus.
7. Kidney disease (acute or chronic, according to physician (Creatinin/Urea/Cystatin-C for Schwartz Calculation)).
8. Hypo-/Hyperthyroidism, unless under stable treatment.
9. Severe Vitamin D insufficiency, unless under stable treatment.
10. Abnormal QT interval.
11. Clinically significant abnormal laboratory values, e.g.
Triglycerides > 400 mg/dl (Salzburg) or > 4,5 mmol/L (Uppsala),
Amylase > 300 U/L (Salzburg) or > 5,1 µkat/L (Uppsala),
Lipase > 180 U/L (Salzburg) or > 15 µkat/L (Uppsala) or
Calcitonin > 11.7 pg/ml (Salzburg) or > 3,4 pmol/L (Uppsala) for females and > 17 pg/ml (Salzburg) or > 5,0 pmol/L (Uppsala) for males.
12. Severe depression, severe anxiety or other psychiatric disorder referred to or undergoing special treatment, as judged by the investigator.
13. Severe sleep apnea (defined clinically).
14. Chronic diseases, as judged by the investigator.
15. Metformin treatment within 3 months prior to screening or concomitant medication influencing blood glucose (e.g. metformin and acarbose), influencing other parameters of metabolic syndrome (e.g. orlistat) or interfering with the investigational medicinal product.
16. Steroid treatment (oral or injected).
17. Concomitant medication addressing attention disorders.
18. Antidepressants that can lead to weight gain, as judged by the investigator.
19. Hypersensitivity to exenatide or to any of the excipients.
20. Pacemaker or metal implant that may interfere with Magnetic Resonance Imaging (MRI).
21. Claustrophobia.
22. Current or prior (within 3 months) participation in another clinical study involving an Investigational Medicinal Product (IMP).
23. A personal or family history of Medullary Thyroid Carcinoma (MTC)
24. A personal or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
BMI SDS (according to WHO). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Adverse events, vital signs (blood pressure and pulse), electrocardiogram (ECG), tympanic body temperature, glucose, clinical chemistry, hematology and urinalysis.
2. Endpoints of insulin secretion and sensitivity derived from Oral Glucose Tolerance Test (OGTT).
3. Glucagon levels at specified time points.
4. Triglycerides, High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), total cholesterol, FFAs, apolipoproteins, uric acid and blood pressure.
5. hs-CRP
6. Bioimpedance assessments to calculate total and regional body composition and Magnetic Resonance Imaging (MRI) assessments of abdominal adipose tissue, organ fat characteristics and morphology (volume of Visceral and abdominal Subcutaneous Adipose Tissue (VAT/SAT) and Liver Fat (LF) content)
7. Waist, hip, upper thigh and neck circumference, waist-to-hip-ratio, sagittal abdominal diameter and skinfold caliper assessments of body fat.
8. s-BMI.
9. Interdisciplinary Adiposity Evaluation kit (AD-EVA), Sleeping habits questionnaire, Self-efficacy and outcome expectations questionnaire (SWE & HEE), Food Frequency Questionnaire (FFQ), Regular meals questionnaire, Portion size questionnaire, Walking test (6 min.), Physical activity questionnaire and Physical activity assessed by accelerometry.
10. U-alpha1-microglobulin (protein HC)/Creatinine and estimated Glomerular Filtration Rate (GFR) according to Schwartz formula.
11. Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), Gamma-Glutamyl Transpeptidase (GGT), Lactate Dehydrogenase (LD) and Bilirubin.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | 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) | Yes |
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) | Yes |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |