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 |
Abnormal or excessive body fat accumulation/excess proportion of total body fat |
|
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 | 20.0 |
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 |
|
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 confirm superiority of liraglutide 3.0 mg vs. placebo, as an adjunct to a reduced-calorie diet and
increased physical activity, on weight loss effectiveness in subjects with overweight or obesity and
type 2 diabetes mellitus (T2DM) treated with a basal insulin and up to 2 oral antidiabetic (OAD)
medications (metformin, glitazone, SGLT-2 inhibitor, alpha glucosidase inhibitor, glinide or sulphonylurea). |
|
E.2.2 | Secondary objectives of the trial |
1. To establish the effects of liraglutide 3.0 mg vs. placebo, as an adjunct to a reduced-calorie diet and increased physical activity, on relevant efficacy endpoints in subjects with overweight or obesity
and T2DM treated with basal insulin and up to 2 OADs (metformin, glitazone, SGLT-2 inhibitor, alpha glucosidase inhibitor, glinide or
sulphonylurea)
2. To establish the safety and tolerability of liraglutide 3.0 mg vs. placebo, as an adjunct to a reducedcalorie diet and increased physical activity, in subjects with overweight or obesity and T2DM
treated with basal insulin and up to 2 OADs (metformin, glitazone, SGLT-2 inhibitor, alpha glucosidase inhibitor, glinide or
sulphonylurea) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed consent obtained before any trial-related activities. Trial-related activities are any
procedures that are carried out as part of the trial, including activities to determine suitability
for the trial
- Diagnosed with type 2 diabetes mellitus
- Treatment with up to 2 OADs (metformin, glitazone, SGLT-2 inhibitor, alpha glucosidase inhibitor, glinide or sulphonylurea),
- Stable treatment with basal insulin (no requirement of minimum or maximum dose) for at least 90 days prior to screening, as judged by the investigator
- HbA1c 6.0-10.0% (both inclusive)
- BMI ≥ 27 kg/m2
- Age ≥ 18 years at the time of signing informed consent |
|
E.4 | Principal exclusion criteria |
- Diagnosis of type 1 diabetes
- Known hypoglycaemic unawareness as indicated by the investigator according to Clarke’s
questionnaire question 8
- Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator
- Unable or unwilling to perform self-monitoring of plasma glucose according to the protocol and to keep a diabetes diary
- Treatment with any hypoglycaemic medications other than OADs and basal insulin within the past 90 days prior to screening
- Treatment with a DPP-IV inhibitor within the past 90 days prior to screening
- Recent history of cardiovascular disease (myocardial infarction or stroke within the past 6 months), severe congestive heart failure (NYHA class III, IV), or second degree or greater heart block
- Personal or family history of Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplasia type 2 (MEN2)
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing
potential and not using an adequate contraceptive method (adequate contraceptive measure
as required by local regulation or practice). For Germany: Only highly effective methods of birth control are accepted (i.e. one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence or vasectomised partner
- Use in past 90 days of medications known to induce significant weight loss (e.g., prescription weight loss medications) or weight gain (e.g., chronic use of oral steroids, second generation antipsychotics)
- History of pancreatitis (acute or chronic)
- History of major depressive disorder within the past 2 years
- Any lifetime history of a suicide attempt
- Inadequately treated blood pressure defined as Grade 3 hypertension or higher (Systolic ≥180 mmHg or diastolic ≥110 mmHg).
- History of malignancy (except for non-melanoma skin cancer) within the past 5 years |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in body weight (%)
2. Proportion of subjects losing at least 5% of baseline body weight |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. from baseline to week 56
2. week 56
|
|
E.5.2 | Secondary end point(s) |
1. Proportion of subjects losing more than 10% of baseline body weight
2. Change in waist circumference
3. Change in HbA1c
4. Change in fasting plasma glucose
5. Change in Short Form-36 (SF-36) v2.0 acute, physical functioning score
6. Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT), physical function domain (5-items) score
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. week 56
2.-6. from baseline to week 56 |
|
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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
European Union |
Israel |
Mexico |
Turkey |
United States |
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 28 |