E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
1. Obesity 2. Diabetes Mellitus, Type 2 |
1. Obesidad 2. Diabetes Mellitus tipo 2 |
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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 |
1. Acumulación excesiva o anormal de grasa en el cuerpo/ Exceso en la proporción total de grasa en el cuerpo 2. Diabetes tipo 2 |
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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 | 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 |
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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 |
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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 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. |
Comparar el efecto de semaglutida subcutánea (s.c.) 2,4 mg una vez a la semana con placebo de semaglutida I/II como complemento de la dieta hipocalórica y del aumento de la actividad física en pacientes con sobrepeso u obesidad y diabetes tipo 2 (DT2) en el peso corporal. |
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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. |
Comparar el efecto de semaglutida s.c. 2,4 mg una vez/sem: 1. con placebo de semagl I/II como complemento de la dieta hipocalórica y del aumento de la actividad física en pacientes con sobrepeso u obesidad y DT2 en:• Factores de riesgo cardiovasc/• Evaluac de resultados clínicos/• Control glucémico 2. Con semaglutida s.c. 1,0 mg una vez/sem como complemento de la dieta hipocalórica y del aumento de la activ. física en pacientes con sobrepeso u obesidad y DT2 en los factores relacionados con el peso corporal. 3.Comparar el efecto de semaglutida s.c. 1,0 mg una vez/sem con placebo de semaglutida I/II como complemento de la dieta hipocalórica y del aumento de la actividad física en pacientes con sobrepeso u obesidad y DT2 en el control de la glucemia. 4.Comparar la seguridad y tolerabilidad de semaglutida s.c. 2,4 mg una vez/ sem con placebo de semaglutida I/II como complemento de la dieta hipocalórica y del aumento de la activ. física en pacientes con sobrepeso u obesidad y DT2. |
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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 |
-Pacientes de ambos sexos, de ≥ 18 años de edad en el momento de la firma del consentimiento informado. -Índice de masa corporal (IMC) ≥ 27 kg/m2. -Antecedentes de al menos un intento fallido de hacer dieta para adelgazar. -Diagnóstico de DT2 (HbA1c del 7 %-10 % (53-86 mmol/mol) (ambos inclusive)) ≥ 180 días antes del día de la selección. |
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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 |
-El paciente refiere una variación del peso corporal > 5 kg en los 90 días anteriores a la selección, con independencia de lo registrado en la historia clínica. -Insuficiencia renal medida como una filtración glomerular estimada (FGe) < 30 ml/min/1,73 m2 (< 60 ml/min/1,73 m2 en los pacientes tratados con SGLT2i ) según la ecuación de creatinina CKD-EPI con arreglo a la definición de KDIGO 2012 en el laboratorio central en la selección. -Retinopatía diabética o maculopatía no controlada y potencialmente inestable. Verificada mediante una oftalmoscopia con dilatación farmacológica de las pupilas realizada por un oftalmólogo o un profesional sanitario de la misma cualificación (p. ej., optometrista) en los 90 días previos a la selección o en el período entre la selección y la aleatorización. |
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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) |
Los criterios de valoración principales que abordan el objetivo principal son: 1. Variación del peso corporal (%). 2. Pacientes que consigan (sí/no) una disminución del peso corporal ≥ 5 % con respecto al momento basal (semana 0). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From baseline (week 0) to week 68 2. After 68 weeks |
1. Entre el momento basal (semana 0) y la semana 68 2. Después de 68 semanas |
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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) |
1. Pacientes que consigan (sí/no): -Disminución del peso corporal ≥ 10 % con respecto al momento basal (semana 0). -Disminución del peso corporal ≥ 15 % con respecto al momento basal (semana 0). 2. Variación de: -Perímetro de la cintura (cm). -Peso corporal (%) (semaglutida s.c. 2,4 mg una vez a la semana comparada con semaglutida s.c. 1,0 mg una vez a la semana). -Hemoglobina A1c (HbA1c) (%, mmol/mol). -Presión arterial sistólica (mm Hg). -Puntuación del funcionamiento físico (SF-36). -Puntuación del dominio de función física (5 ítems) (IWQoL-Lite para CT). 3. Cambios en: - Peso corporal (kg) - IMC(kg/sqm) - HbA1c (%, mmol/mol) (semaglutide s.c. 1.0 mg una vez a la semana frente a semaglutida placebo I/II) - Glucemia plasmática en ayunas (GPA) (mg/dL) - Insulina en suero en ayunas (mIU/L) - Presión sanguínea diastólica (mmHg) - Lípidos (mg/dL) - Colesterol total - Lipoproteína de alta densidad (colesterol HDL) - Lipoproteína de baja densidad (colesterol LDL) - Lipoproteína de muy baja densidad (colesterol VLDL) - Ácidos grasos libres (AGL) - Triglicéridos - Proteína C reactiva de alta sensibilidad (hsCRP) (mg/L) - Actividad del Inhibidor del activador del plasminógeno-1 (PAI-1) (AU/mL) - SF-36 - puntuación rol físico - puntuación dolor corporal - puntuación salud general - puntuación vitalidad - puntuación función social - puntuación rol emocional - puntuación salud mental - resumen componente físico - resumen componente mental - IWQoL-Lite for CT - puntuación dominio del dolor/malestar - puntuación dominio psicosocial - puntuación total 4. Sujetos que consigan (si/no): - Respondedor según definición del valor para la puntuación del funcionamiento físico (SF-36). - Respondedor según definición del valor para la puntuación del dominio de la función física (5-items) IWQoL-Lite for CT - HbA1c < 7.0% (53 mmol/mol) - HbA1c ≤ 6.5% (48 mmol/mol) 5. Número de acontecimientos adversos con tratamientos emergentes (TEAEs) 6. Número de acontecimientos adversos graves (SAEs) 7. Número de episodios de hipoglucemia sintomáticos confirmados por glucosa en sangre o graves con tratamientos emergentes 8. Cambios en: - Pulso (ppm) - Amylasa (U/L) - Lipasa (U/L) - Calcitonina (ng/L) |
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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 |
1. Después de 68 semanas 2. Entre el momento basal (semana 0) y la semana 68 3. Entre el momento basal (semana 0) y la semana 68 4. Después de 68 semanas 5. – 7. Entre el momento basal (semana 0) y la semana75 8. Entre el momento basal (semana 0) y la semana 68 |
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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 | 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 |
Tolerability |
Tolerabilidad |
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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 |
Doble enmascaramiento |
Double dummy |
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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 |
Semaglutida 1,34 mg |
Semaglutide 1.34 mg |
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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 | 7 |
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 |
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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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LVLS |
UVUS (Última visita del ultimo sujeto) |
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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 | 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 |