E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
1. Obesity
2. Diabetes Mellitus, Type 2 |
|
E.1.1.1 | Medical condition in easily understood language |
1. Abnormal or excessive body fat accumulation/excess proportion of total body fat
2. Type 2 diabetes |
|
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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 compare the effect of semaglutide subcutaneous (s.c.) 2.4 mg once-weekly versus semaglutide placebo I/II as an adjunct to a reduced-calorie diet and increased physical activity in subjects with overweight or obesity and type 2 diabetes (T2D) on body weight. |
|
E.2.2 | Secondary objectives of the trial |
To compare the effect of semaglutide s.c. 2.4 mg once-weekly:
1. versus semaglutide placebo I/II as an adjunct to a reduced-calorie diet and increased physical activity in subjects with overweight or obesity and T2D on:
- Cardiovascular risk factors
- Clinical Outcome Assessments
- Glycaemic control
2. versus semaglutide s.c. 1.0 mg once-weekly as an adjunct to reduced-calorie diet and increased physical activity in subjects with overweight or obesity and T2D on factors related to body weight.
3. To compare the effect of semaglutide s.c. 1.0 mg once-weekly versus semaglutide placebo I/II as an adjunct to reduced-calorie diet and increased physical activity in subjects with overweight or obesity and T2D on glycaemic control.
4. To compare the safety and tolerability of semaglutide s.c. 2.4 mg once-weekly versus semaglutide placebo I/II as an adjunct to reduced-calorie diet and increased physical activity in subjects with overweight or obesity and T2D. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age ≥ 18 years at the time of signing informed consent.
- Body Mass Index (BMI) ≥ 27 kg/sqm
- History of at least one self-reported unsuccessful dietary effort to lose body weight
- Diagnosed with T2D (HbA1c 7-10% (53-86 mmol/mol) (both inclusive)) ≥ 180 days prior to the day of screening |
|
E.4 | Principal exclusion criteria |
- A self-reported change in body weight > 5 kg (11 lbs) within 90 days before screening irrespective of medical records
- Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of < 30 mL/min/1.73 sqm (< 60 ml/min/1.73 sqm in subjects treated with SGLT2i ) according to CKDEPI creatinine equation as defined by KDIGO 2012 by the central laboratory at screening
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a
pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to screening or in the period between screening and randomisation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints addressing the primary objective:
1. Change in body weight (%)
2. Subjects who achieve body weight reduction ≥ 5% from baseline (week 0) (yes/no) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From baseline (week 0) to week 68
2. After 68 weeks |
|
E.5.2 | Secondary end point(s) |
1. Subjects who achieve (yes/no):
- Body weight reduction ≥ 10% from baseline (week 0)
- Body weight reduction ≥ 15% from baseline (week 0)
2. Change in:
- Waist circumference (cm)
- Body weight (%) (semaglutide s.c. 2.4 mg once-weekly versus semaglutide s.c. 1.0
mg once-weekly)
- Hemoglobin A1c (HbA1c) (%, mmol /mol)
- Systolic blood pressure (mmHg)
- Physical functioning score (SF-36)
- Physical function domain (5-items) score (IWQoL-Lite for CT)
3. Change in:
- Body weight (kg)
- BMI (kg/sqm)
- HbA1c (%, mmol/mol) (semaglutide s.c. 1.0 mg once-weekly versus semaglutide placebo I/II)
- Fasting plasma glucose (FPG) (mg/dL)
- Fasting serum insulin (mIU/L)
- Diastolic blood pressure (mmHg)
- Lipids (mg/dL)
- Total cholesterol
- High density lipoprotein (HDL) cholesterol
- Low density lipoprotein (LDL) cholesterol
- Very low density lipoprotein (VLDL) cholesterol
- Free fatty acids (FFA)
- Triglycerides
- High sensitivity C-Reactive Protein (hsCRP) (mg/L)
- Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/mL)
- SF-36
- role-physical score
- bodily pain score
- general health score
- vitality score
- social functioning score
- role-emotional score
- mental health score
- physical component summary
- mental component summary
- IWQoL-Lite for CT
- pain/discomfort domain score
- psychosocial domain score
- total score
4. Subjects who achieve (yes/no):
- Responder definition value for SF-36 physical functioning score
- Responder definition value for IWQoL-Lite for CT physical function domain (5-items) score
- HbA1c < 7.0% (53 mmol/mol)
- HbA1c ≤ 6.5% (48 mmol/mol)
5. Number of treatment-emergent adverse events (TEAEs)
6. Number of serious adverse events (SAEs)
7. Number of treatment emergent severe or blood glucose confirmed symptomatic
hypoglycaemia episodes
8. Change in:
- Pulse (bpm)
- Amylase (U/L)
- Lipase (U/L)
- Calcitonin (ng/L) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 68 weeks
2. From baseline (week 0) to week 68
3. From baseline (week 0) to week 68
4. After 68 weeks
5. – 7. From baseline (week 0) to week 75
8. From baseline (week 0) to week 68 |
|
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
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 | Yes |
E.8.2.3.1 | Comparator description |
|
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
| 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Algeria |
Argentina |
Canada |
European Union |
India |
Japan |
Russian Federation |
South Africa |
United Arab Emirates |
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 | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |