E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Diabetes Melitus, tipo 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Diabetes tipo 2 |
|
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 | 16.0 |
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 |
|
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 once-weekly dosing of two dose levels of semaglutide versus sitagliptin 100 mg once-daily on glycaemic control after 56 weeks of treatment |
Comparar el efecto de la administración una vez por semana de dos niveles de dosis de semaglutida con el de 100 mg de sitagliptina una vez al día en el control de la glucemia después de 56 semanas de tratamiento |
|
E.2.2 | Secondary objectives of the trial |
To compare the effect of once-weekly dosing of two dose levels of semaglutide versus sitagliptin 100 mg once-daily after 56 weeks of treatment on: - Inducing and maintaining weight loss - Other parameters of efficacy, safety and tolerability |
Comparar el efecto de la administración una vez por semana de dos niveles de dosis de semaglutida con el de 100 mg de sitagliptina una vez al día tras 56 semanas de tratamiento en: - La inducción y el mantenimiento de la pérdida de peso - Otros parámetros de eficacia, seguridad y tolerabilidad |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age higher or equal to 18 years at the time of signing informed consent. For Japan only: Age higher or equal to 20 years - Subjects diagnosed with type 2 diabetes and on stable treatment in a period of 90 days prior to screening with either metformin higher or equal to 1500 mg (or maximum tolerated dose), pioglitazone higher or equal to 30 mg (or maximum tolerated dose), rosiglitazone higher or equal to 4 mg (or maximum tolerated dose) or a combination of either metformin/pioglitazone or metformin/rosiglitazone (doses as for individual therapies). Stable is defined as unchanged medication and unchanged dose. - HbA1c 7.0 ? 10.5 % (53 ? 91 mmol/mol) (both inclusive) |
- Pacientes de ambos sexos de edad mayor o igual a 18 años en el momento de la firma del consentimiento informado. Solo en Japón: Edad mayor o igual a 20 años. - Sujetos con diagnóstico de diabetes tipo 2 y en tratamiento estable durante un período de 90 días antes de la selección con dosis mayor o igual a 1500 mg de metformina (o la dosis máxima tolerada), dosis mayor o igual a 30 mg de pioglitazona (o la dosis máxima tolerada), dosis mayor o igual a 4 mg de rosiglitazona (o la dosis máxima tolerada) o una combinación de metformina/pioglitazona o de metformina/rosiglitazona (en dosis iguales a las terapias individuales). Se define estable como medicación sin cambios y dosis sin cambios. - HbA1c 7,0-10,5 % (53-91 mmol/mol) (ambos inclusive). |
|
E.4 | Principal exclusion criteria |
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using an adequate contraceptive method throughout the trial including the 5 weeks follow-up period (adequate contraceptive measures as required by local law or practice) - Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject?s safety or compliance with the protocol - Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (? 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value ? 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as eGFR < 60 ml/min/1.73 m2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association (NYHA) class IV |
- Mujeres en edad fértil embarazadas o amamantando o que pretendan quedarse embarazadas o no utilicen un método anticonceptivo adecuado durante todo el ensayo, incluido el período de seguimiento de cinco semanas (las medidas anticonceptivas adecuadas exigidas por la legislación o la práctica locales) - Cualquier trastorno crónico o enfermedad grave que, en opinión del investigador, pueda poner en peligro la seguridad del sujeto o el cumplimiento del protocolo - Tratamiento con fármacos hipoglucemiantes distintos del indicado en los criterios de inclusión en un período de 90 días antes de la selección. Una excepción es el tratamiento a corto plazo (menor o igual a 7 días en total) con insulina relacionado con enfermedad intercurrente - Antecedentes de pancreatitis crónica o idiopática aguda - Valor de calcitonina mayor o igual a 50 ng/l (pg/ml) en la selección - Antecedentes personales o familiares de carcinoma medular de tiroides (CMT) o síndrome de neoplasias endocrinas múltiples tipo 2 (MEN 2) - Disfunción renal definida como una FGe menor a 60 ml/min/1,73 m2 según la fórmula de la modificación de la dieta en enfermedad renal (MDRD) (versión de cuatro variables) - Episodio coronario o cerebrovascular agudo en los 90 días previos a la aleatorización - Insuficiencia cardíaca, clase IV de la New York Heart Association (NYHA) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c |
Cambio de la HbA1c |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 56 |
desde el momento basal a la semana 56 |
|
E.5.2 | Secondary end point(s) |
Confirmatory efficacy endpoint: 1. Change in body weight
Supportive efficacy endpoints: Change in: 2. Fasting Plasma Glucose (FPG) 3. Systolic and diastolic blood pressure 4. Patient reported outcome (PRO) questionnaire Diabetes Treatment Satisfaction Questionnaire status (DTSQs) These endpoints will be evaluated as the mean treatment differences.
Subjects who achieve (yes/no): 5. HbA1c less or equal to 6.5% (48 mmol/mol) American Association of Clinical Endocrinologists (AACE) target This endpoint will be evaluated as the odds ratio between treatments. |
Criterio de eficacia confirmatorio: 1. Cambio del peso corporal
Criterios de valoración de la eficacia de apoyo: Cambio en: 2. La glucemia plasmática en ayunas (GPA) 3. La presión arterial sistólica y diastólica 4. El cuestionario de resultados comunicados por los pacientes (RCP) del estado del Cuestionario de satisfacción con el tratamiento de la diabetes (DTSQs) Estos criterios de valoración se evaluarán como las diferencias medias entre tratamientos.
Sujetos que consigan (sí/no): - El objetivo de la American Association of Clinical Endocrinologists (AACE) de HbA1c menor o igual a 6,5 % (48 mmol/mol). Este criterio de valoración se evaluará como el cociente de probabilidad entre los tratamientos. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Confirmatory efficacy endpoint: 1. From baseline to week 56
Supportive efficacy endpoints: 2.-4. From baseline to week 56
5. After 56 weeks treatment |
Criterio de eficacia confirmatorio: 1. desde el momento basal a la semana 56
Criterios de valoración de la eficacia de apoyo: 2. desde el momento basal a la semana 56 3. Tras 56 semanas de tratamiento |
|
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 | Yes |
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 |
|
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 | Yes |
E.8.1.7.1 | Other trial design description |
con doble simulación |
Double dummy |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 41 |
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 |
European Union |
Argentina |
Hong Kong |
India |
Japan |
Mexico |
Norway |
Russian Federation |
South Africa |
Thailand |
Turkey |
Ukraine |
|
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
|
LVLS |
UVUP (Última Visita del Último Paciente) |
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | 16 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 16 |