E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, type 2 |
Diabetes Mellitus, Tipo 2 |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
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 | 21.1 |
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 | 100000004861 |
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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 confirm that efficacy as measured by change from baseline to week 40 in HbA1c (% point) of OW (once weekly) semaglutide s.c. 2.0 mg as add-on to dose-reduced insulin glargine is not unacceptably worse (i.e., non-inferior) to that of titrated insulin glargine on change from baseline to week 40 in HbA1c (%-point) in participants with T2D and overweight treated with 40 units or less of insulin glargine per day. Non-inferiority is assessed based on the clinically acceptable margin of 0.3%-point for the mean treatment difference in HbA1c. |
Confirmar que la eficacia, determinada por el cambio de la HbA1c (en %) desde el momento basal a la semana 40, de 2,0 mg de semaglutida SC 1 vez/semana añadidos a insulina glargina en dosis reducida no es inaceptablemente peor (es decir, no es inferior) a la de la insulina glargina ajustada en el cambio desde el momento basal hasta la semana 40 de la HbA1c (en %) en los participantes con DT2 y sobrepeso tratados con 40 U o menos de insulina glargina al día. La no inferioridad se valora basándose en el margen clínicamente aceptable del 0,3% para la diferencia media entre los tratamientos en la HbA1c. |
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E.2.2 | Secondary objectives of the trial |
1. To confirm superiority of OW semaglutide s.c. 2.0 mg as add-on to dose-reduced insulin glargine versus titrated insulin glargine on:
a. change from baseline to week 40 in body weight (kg) and HbA1c (%) in participants with T2D and overweight treated with 40 units or less of insulin glargine per day.
b. change from baseline to week 40 in DTSQc score in participants with T2D and overweight treated with 40 units or less of insulin glargine per day.
c. relative change from baseline to week 40 in daily insulin dose (%) in participants with T2D and overweight treated with 40 units or less of insulin glargine per day.
2. To compare the effect of OW semaglutide s.c. 2.0 mg as add-on to dose-reduced insulin glargine versus titrated insulin glargine on insulin requirements, glycaemic control, hypoglycaemia, and patient reported outcome in participants with T2D and overweight treated with 40 units or less of insulin glargine per day. |
1. Confirmar superioridad 2,0 mg Sema. SC 1 V/S añadidos a I. glargina en dosis reducida en comparación con I. glargina ajustada en: a. cambio desde momento basal a semana 40 del peso corporal (kg) y HbA1c (%) de participantes con DT2 y sobrepeso tratados con 40U o menos de I. glargina al día b. cambio desde momento basal a semana 40 de puntuación del Cuestionario de satisfacción con el tratamiento de la diabetes (DTSQc) en participantes con DT2 y sobrepeso tratados con 40 U o menos de I. glargina al día. c. cambio relativo desde momento basal a semana 40 de la dosis diaria de insulina (%) en participantes con DT2 y sobrepeso tratados con 40U o menos de I. glargina al día 2. Comparar efecto de 2,0 mg Sema SC 1 V/S añadidos a I. glargina en dosis reducida en comparación con I. glargina ajustada según requerimientos de insulina, control glucémico, hipoglucemia y resultado de cuestionarios pacientes en participantes con DT2 y sobrepeso tratados con 40U o menos de I. glargina por día |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosed with T2D mellitus greater than or equal to 180 days before screening. - HbA1c of 7-9% (53−75 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening. - Body mass index (BMI) greater than or equal to 25 kg/m^2 on the day of screening. - Stable daily dose(s) greater than or equal to 90 days before screening of any of the following anti-diabetic drugs or combination regimens: - Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. - Any metformin combination formulation greater than or equal to 1500 mg or maximum tolerated or effective dose. The treatment can be with or without SGLT-2 inhibitors. - Treated with once daily insulin glargine U100 injections less than or equal to 40 units/day greater than or equal to 90 days before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed. |
- Diagnóstico de DT2 mellitus 180 días o más previo a la selección. - Valor de HbA1c de 7-9% (53-75 mmol/mol) (ambos inclusive) valorada por el laboratorio central el día de la selección. - Índice de masa corporal (IMC) mayor o igual a 25 kg/m2 el día de la selección. - Dosis diaria estable 90 días o más antes de la selección de cualquiera de los antidiabéticos o pautas combinadas siguientes: - Cualquier formulación de metformina mayor o igual de 1500 mg o la dosis máxima tolerada o eficaz. - Cualquier formulación combinada de metformina mayor o igual de 1500 mg o la dosis máxima tolerada o eficaz. El tratamiento puede ser con o sin inhibidores del SGLT-2. - Tratamiento con inyecciones diarias de insulina glargina U100 menor o igual a 40 unidades/día durante 90 o más días, antes de la selección. Se permite el tratamiento con insulina en bolo en un corto plazo durante un máximo de 14 días antes de la selección. |
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E.4 | Principal exclusion criteria |
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
- Potentially missed diagnosis of Type 1 diabetes (T1D) or latent autoimmune diabetes in adults (LADA) verified by C-peptide less than 0.5 nmol/L (1.5 ng/mL) or antibodies to glutamic acid decarboxylase (anti-GAD) greater than 5 units/mL, as measured by the central laboratory at screening.
- Presence or history(a) of pancreatitis (acute or chronic). - Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 30 mL/min/1.73 m2 at screening as defined by KDIGO 2012 classification. - Any episodes(a) of diabetic ketoacidosis within 90 days before screening. - Known hypoglycaemic unawareness as indicated by the investigator according to Clarke’s questionnaire question.
(a) As declared by the participant or in the medical records |
- Retinopatía o maculopatía diabética no controlada y potencialmente inestable. Verificada mediante exploración del fondo de ojo en los 90 días previos a la selección o en el período entre la selección y la aleatorización. La dilatación farmacológica de la pupila es un requisito, a menos que se utilice una cámara fotográfica digital del fondo de ojo especificada para exploración sin dilatación. - Diagnóstico de diabetes de tipo 1 (DT1) o diabetes autoinmune latente en adultos (DALA) posiblemente omitido, indicado por valores de péptido C menores a 0,5 nmol/l (1,5 ng/ml) o de anticuerpos contra la descarboxilasa del ácido glutámico (anti-GAD) mayores a 5 unidades/ml, determinados por el laboratorio central en la selección. - Presencia o antecedentes de pancreatitis (aguda o crónica). - Disfunción renal determinada por un valor de filtración glomerular estimada menor de 30 ml/min/1,73 m2 en la selección, definido en la clasificación KDIGO 2012. - Cualquier episodio de cetoacidosis diabética en los 90 días previos a la selección. - Conocimiento por el investigador, de acuerdo con la pregunta 8 del cuestionario de Clarke, de hipoglucemias desapercibidas. a Declarados por el participante o en la historia clínica. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in HbA1c |
1. Cambio en HbA1c |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From baseline (week 0) to end of treatment (week 40) |
1. Desde el momento basal (semana 0) al final del tratamiento (semana 40) |
|
E.5.2 | Secondary end point(s) |
1. Change in body weight 2 Relative change in daily insulin dose 3. Change in HbA1c 4. Score of Diabetes Treatment Satisfaction Questionnaire – change version (DTSQc) 5. Participants achieving: Insulin dose = 0 U 6. Participants achieving: Insulin dose reduced from baseline by at least 50% 7. Participants achieving: HbA1c < 7% 8. Number of severe hypoglycaemic episodes (level 3) 9. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter) 10. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) 11. Participants achieving all of the following targets: - HbA1c reduced from baseline by at least 0.3%-points - Insulin dose reduced from baseline - No hypoglycaemic episodes (< 3.9 mmol/L (70 mg/dL) confirmed by BG meter) - No weight gain 12. Change in score of Diabetes Treatment Satisfaction Questionnaire – status version (DTSQs) |
1. Cambio del peso corporal 2. Cambio relativo de la dosis diaria de insulina 3. Cambio en HbA1c 4. Puntuación del Cuestionario de satisfacción con el tratamiento de la diabetes – versión cambio (DTSQc) 5. Participantes que lograron: Dosis de insulina = 0 U 6. Participantes que lograron: La dosis de insulina se redujo con respecto al valor inicial en al menos 50% 7. Participantes que lograron: HbA1c menor de 7% 8. Número de episodios de hipoglucemia grave (nivel 3) 9. Número de episodios hipoglucémicos clínicamente significativos (nivel 2) (< 3,0 mmol/L (54 mg/dL) confirmado por glucómetro) 10. Número de episodios hipoglucémicos clínicamente significativos (nivel 2) (<3,0 mmol/L (54 mg/dL), confirmado por glucómetro) o episodios de hipoglucemia grave (nivel 3) 11. Participantes que lograron todos los siguientes objetivos: - HbA1c reducida desde el valor inicial en al menos 0,3% puntos - Dosis de insulina reducida desde el inicio - Ningún episodio de hipoglucemia (< 3,9 mmol/L (70 mg/dL) confirmados por glucómetro) - Sin aumento de peso 12. Cambio en la puntuación del Cuestionario de Satisfacción con el Tratamiento de la Diabetes –versión estado (DTSQs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.-3, 8-10. From baseline (week 0) to end of treatment (week 40) 4.-7, 11-12. At end of treatment (week 40) |
1.-3, 8-10. Desde el momento basal (semana 0) al final del tratamiento (semana 40) 4.-7, 11-12. Al final del tratamiento (semana 40) |
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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 | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Insulin glargine (titrated) |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Russian Federation |
South Africa |
Ukraine |
United States |
European Union |
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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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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 | 3 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 6 |