E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus |
Diabetes Mellitus tipo 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes mellitus |
Diabetes Mellitus 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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 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 demonstrate the non-inferiority of H0E901-U300 to Lantus, in change of glycated hemoglobin A1c (HbA1c) |
Demostrar la no inferioridad de HOE901-U300 en comparación con Lantus en la modificación de la hemoglobina glucosilada A1c (HbA1c) desde el momento basal hasta la Semana 26. |
|
E.2.2 | Secondary objectives of the trial |
To demonstrate the superiority of H0E901-U300 in comparison with Lantus in: - Percentage of patients with at least one severe and/or confirmed (by plasma glucose ?70mg/dL [3.9mmol/L]) hypoglycemia event from 22:00 to 08:59 next morning - Percentage of patients with at least one nocturnal (from 00:00?05:59) severe and/or confirmed (?70mg/dL [3.9mmol/L]) hypoglycemia event - Percentage of patients with at least one severe and/or confirmed (by plasma glucose ?70mg/dL [3.9mmol/L]) hypoglycemia event occurring at any time of day - HbA1c change |
Demostrar la superioridad de HOE901-U300 en comparación con Lantus en:
? El porcentaje de pacientes con al menos un episodio de hipoglucemia severa y/o confirmada (mediante valores de glucosa plasmática 70 mg/dl [3,9 mmol/l]) desde las 22:00 hasta las 08:59 de la mañana siguiente a lo largo de 26 semanas de tratamiento
? El porcentaje de pacientes con al menos un episodio de hipoglucemia nocturna (desde las 00:00 hasta las 05:59) severa y/o confirmada ( 70 mg/dl [3,9 mmol/l]) a lo largo de 26 semanas de tratamiento
? El porcentaje de pacientes con al menos un episodio de hipoglucemia severa y/o confirmada (mediante valores de glucosa plasmática 70 mg/dl [3,9 mmol/l]) ocurrido en cualquier momento del día, a lo largo de 26 semanas de tratamiento
? Cambio en la HbA1c desde el momento basal hasta la Semana 26 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients ?65 years old with type 2 diabetes mellitus, inadequately controlled on antidiabetic regimens either including no insulin, or with basal insulin as their only insulin. Signed informed consent. |
? Pacientes sup o igual a 65 años con diabetes mellitus tipo 2, controlados insuficientemente con tratamientos farmacológicos antidiabéticos noinsulínicos o con insulina basal como única insulina y
? Consentimiento informado firmado |
|
E.4 | Principal exclusion criteria |
HbA1c at screening visit: - <7.0% or >10.0% for patients taking basal insulin. - <7.5% or >11.0% for insulin-naïve patients. History of type 2 diabetes mellitus for less than 1 year before screening. Patients not on stable basal insulin dose (±10% in the last 8 weeks prior to screening visit). Change in dose of antidiabetic treatment or initiation of new glucose-lowering medications in the last 8 weeks prior to screening. Chronic (>10 days continuous use in previous 6 months) use of bolus insulin injections, whether given separately or as part of a combination with basal insulin, eg, premix insulin; For insulin-naïve individuals: current or previous insulin use except for a maximum of 10 consecutive days (e.g. acute illness, surgery) during the last year prior to screening. Cognitive disorder and dementia assessed clinically and by Mini?Mental State Examination (MMSE) score <24, or any neurologic disorder that will likely affect the patient?s ability to follow the study procedure. The patient will be eligible despite an MMSE score <24 if the investigator determines that the low score reflects educational or cultural background and not dementia as long as the patient is otherwise able to meet the study requirements. Patients who have end-stage renal disease (<15 mL/min/1.73m^2, per estimated Glomerular filtration rate [eGFR] measurement by Modification of Diet in Renal Disease [MDRD]). |
? HbA1c en la visita de selección:
- < 7,0 % o > 10,0 % para pacientes que toman insulina basal,
- < 7,5 % o > 11,0 % para pacientes no insulinizados
? Pacientes sin una dosis de insulina basal estable (± 10 % en las últimas 8 semanas antes de la visita de selección); cambio en la dosis del tratamiento antidiabético no-insulínico o inicio de nuevos fármacos hipoglucemiantes en las últimas 8 semanas antes de la selección; ? Uso crónico (> 10 días de uso continuo en los últimos 6 meses) de inyecciones de insulina en bolo, administradas por separado o como parte de una combinación con insulina basal, por ejemplo, insulina premezclada; en el caso de pacientes no insulinizados: uso actual o previo de insulina excepto durante un máximo de 10 días consecutivos (p. ej., enfermedad aguda, cirugía) durante el último año antes de la selección;
? Trastorno cognitivo y demencia evaluados clínicamente y por una puntuación < 24 en el Mini-Examen del Estado Mental (Mini-Mental State Examination, MMSE) o cualquier trastorno neurológico que probablemente afectará a la capacidad del paciente para seguir el procedimiento del estudio. El paciente será apto a pesar de tener una puntuación < 24 en el MMSE si el investigador determina que la baja puntuación refleja su bagaje educativo o cultural y no demencia, siempre que el paciente sea por lo demás capaz de cumplir los requisitos del estudio; ? Pacientes con enfermedad renal crónica terminal (< 15 ml/min/1,73 m2, conforme a la medición de la tasa de filtración glomerular estimada (TFGe) utilizando la fórmula de la Modificación de la Dieta en la Enfermedad Renal (Modification of Diet in Renal Disease, MDRD). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c from baseline |
Variación de la HbA1c |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline, week 26 |
desde el momento basal hasta la Semana 26. |
|
E.5.2 | Secondary end point(s) |
1 - Incidence (% of patients) of severe and/or confirmed (by plasma glucose ?70mg/dL [3.9mmol/L]) hypoglycemia event (symptomatic or asymptomatic) from 22:00 to 08:59 next morning over 26 weeks of treatment 2 - Incidence (% of patients) of nocturnal (from 00:00 to 05:59) severe and/or confirmed (?70 mg/dL [3.9mmol/L]) hypoglycemia (symptomatic or asymptomatic) over 26 weeks of treatment 3 - Incidence (% of patients) of severe and/or confirmed (by plasma glucose ?70mg/dL [3.9mmol/L]) hypoglycemia (symptomatic or asymptomatic), occurring at any time of day, over 26 weeks of treatment 4 - Percentage of patients with HbA1c (a) <7.5% (b), <7.0%, at Week 26 5 - Percentage of eligible patients with HbA1c (a) <7.5%, (b) <7.0%, at Week 26, with no severe and/or confirmed (by plasma glucose ?70mg/dL [3.9mmol/L]) hypoglycemia event over 26 weeks of treatment 6 - Change in fasting plasma glucose (FPG) from baseline to Week 26 7 - Change in Patient Report Outmcome (PRO) instruments scores from baseline to Week 26 8 - Percentage of patients requiring rescue therapy over the 26 weeks of treatment |
1. Incidencia (% de pacientes) de episodios de hipoglucemia (sintomática o asintomática) severa y/o confirmada (mediante valores de glucosa plasmática 70 mg/dl [3,9 mmol/l]) desde las 22:00 hasta las 08:59 de la mañana siguiente a lo largo de 26 semanas de tratamiento. 2. Incidencia (% de pacientes) de hipoglucemia nocturna (desde las 00:00 hasta las 05:59) (sintomática o asintomática) severa y/o confirmada (mediante valores de glucosa plasmática 70 mg/dl [3,9 mmol/l]) a lo largo de 26 semanas de tratamiento. 3. Incidencia (% de pacientes) de hipoglucemia (sintomática o asintomática) severa y/o confirmada (mediante valores de glucosa plasmática 70 mg/dl [3,9 mmol/l]), ocurrida en cualquier momento del día, a lo largo de 26 semanas de tratamiento. 4. Porcentaje de pacientes con HbA1c (a) < 7,5 % (b) < 7,0 %, en la Semana 26. 5. Porcentaje de pacientes con HbA1c (a) < 7,5 % (b) < 7,0 %, en la Semana 26, sin episodios de hipoglucemia severa y/o confirmada (mediante valores de glucosa plasmática 70 mg/dl [3,9 mmol/l]) a lo largo de 26 semanas de tratamiento. 6. Variación de la GPA desde el momento basal hasta la Semana 26. 7. Cambio en las puntuaciones de RNP desde el momento basal hasta la Semana 26. 8. Porcentaje de pacientes que requieren tratamiento de rescate a lo largo de 26 semanas de tratamiento. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - 2 - 3 - 4 - 5 - 8 - week 26
6 - 7 - baseline, week 26 |
1,2,3,4,5 y 8: a la semana 26 6 y 7: desde el momento basal hasta la Semana 26. |
|
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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Colombia |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Mexico |
Peru |
Poland |
Romania |
Spain |
Sweden |
United Kingdom |
|
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
|
LVLS |
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 | |
E.8.9.1 | In the Member State concerned months | 26 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 26 |