E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 diabetes mellitus |
Diabetes Mellitus tipo I |
|
E.1.1.1 | Medical condition in easily understood language |
Type 1 diabetes mellitus |
Diabetes Mellitus tipo I |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 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 efficacy of HOE901-U300 to Lantus in terms of glycated hemoglobin (HbA1c) |
Comparar la eficacia de una nueva formulación de insulina glargina (HOE901-U300) con Lantus en cuanto al cambio de hemoglobina glucosilada A1c (HbA1c) |
|
E.2.2 | Secondary objectives of the trial |
-To compare HOE901-U300 and Lantus in terms of: -Percentage of patients reaching target HbA1c and fasting plasma glucose (FPG). -To assess the safety of HOE901-U300 including analysis of events of hypoglycemia, events of hyperglycemia with ketosis, and development of anti-insulin-antibodies. |
Comparar HOE901-U300 y Lantus en cuanto al: - Porcentaje de pacientes que logran el valor deseado de HbA1c (<7,5 %) y en glucosa plasmática en ayunas - Evaluar la seguridad de HOE901-U300, incluyendo el análisis de episodios de hipoglucemia, episodios de hiperglucemia con cetosis y el desarrollo de anticuerpos antiinsulina; |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Children and adolescents with type 1 diabetes mellitus (T1DM) for at least 1 year confirmed by typical symptoms at diagnosis and/or by antibody testing (presence of anti-GAD [glutamic acid decarboxylase] or anti-IA2 [islet antigen 2/tyrosine phosphatase] or anti-islet cell antibodies) and/or clinical features (eg, history of ketoacidosis). -Signed written informed consent obtained from parent(s)/legal guardian and written or oral assent obtained from patient. |
- Niños y adolescentes con DMT1 desde hace al menos 1 año confirmada por síntomas típicos en el momento del diagnóstico y/o por pruebas de anticuerpos (presencia de anticuerpos anti-GAD [glutamic acid decarboxylase (descarboxilasa del ácido glutámico)], o anti-IA2 [islet antigen 2/tyrosine phophatase (antígeno de islote-2/tirosina fosfatasa)] o anticuerpos contra las células de los islotes) y/o signos clínicos (p. ej., antecedentes de cetoacidosis); - Consentimiento informado por escrito firmado obtenido de su(s) padre(s)/tutor(es) legal(es) y asentimiento escrito u oral obtenido del paciente. |
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E.4 | Principal exclusion criteria |
-Age <6 years and ?18 years. -Less than 1 year on insulin treatment prior to screening visit. -Less than 6 months on basal plus mealtime insulin and self-monitoring of blood glucose prior to screening visit. -Patients using premix insulins in the last 3 months before screening visit or patients using human regular insulin as mealtime insulin in the last 3 months before screening visit. -Use of an insulin pump in the last 6 months before screening visit or plans to switch to pump within the next 6 months after screening visit. -No willingness to inject insulin glargine (Lantus or HOE901 [U300]) once daily. -HbA1c <7.5% or >10% at screening. -Initiation of any glucose-lowering medications in the last 3 months before screening visit. -Hospitalization or care in the emergency ward for diabetic ketoacidosis or history of severe hypoglycemia (as defined by need for glucagon or IV glucose) and accompanied by seizure and/or unconsciousness and/or coma in the last 3 months prior to screening visit. -Postmenarchal girls not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy. Abstinence from sexual intercourse will be considered as an acceptable form of birth control. -Pregnant or breast-feeding adolescents, or adolescents who intend to become pregnant during the study period, or who are at risk of getting pregnant due to any psychosocial reason during the study period. |
- Edad inferior a 6 años y mayor o igual a 18 años; - Menos de 1 año de tratamiento con insulina antes de la visita de selección; - Menos de 6 meses con insulina basal más insulina prandial y autocontrol de la glucemia antes de la visita de selección; - Pacientes que utilizasen insulinas premezcladas en los últimos 3 meses antes de la visita de selección o pacientes que utilizasen insulina humana regular como insulina prandial en los últimos 3 meses antes de la visita de selección; - Uso de una bomba de insulina en los últimos 6 meses antes de la visita de selección o intención de cambiar a la bomba en los 6 meses siguientes a la visita de selección; - Falta de disposición para inyectar la insulina glargina (Lantus o HOE901-U300) una vez al día; - HbA1c <7,5 % o >10 % en la selección; - Inicio de cualquier medicación hipoglucemiante en los últimos 3 meses antes de la visita de selección; - Hospitalización o visita a urgencias por cetoacidosis diabética o antecedentes de hipoglucemia severa (definida por la necesidad de glucagón o glucosa intravenosa (i. v.)) y acompañada por convulsiones y/o inconsciencia y/o coma en los últimos 3 meses antes de la visita de selección; - Niñas posmenárquicas que no estén protegidas por método(s) anticonceptivo(s) de alta eficacia y/o que no estén dispuestas o a las que no se pueda realizar pruebas de embarazo. La abstinencia de relaciones sexuales se considerará una forma aceptable de anticonceptivo; - Adolescentes embarazadas o en periodo de lactancia o adolescentes que pretendan quedarse embarazadas durante el periodo de estudio o que estén en riesgo de quedarse embarazadas debido a cualquier motivo psicosocial durante el periodo de estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c |
Cambio desde la basal en HbA1c |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline; Week 26 |
Basal; semana 26 |
|
E.5.2 | Secondary end point(s) |
1- Percentage of patients with HbA1c values of <7.5% without any episode of severe and/or documented (SMPG <54 mg/dL; 3.0 mmol/L) symptomatic hypoglycemia during the last 3 months of the main 6-month on-treatment period 2- Change from baseline in FPG 3- Percentage of patients with FPG of ?130 mg/dL (7.2 mmol/L) without any episode of severe and/or documented (SMPG ?54 mg/dL; 3.0 mmol/L) symptomatic hypoglycemia during the last 3 months of the main 6-month 4- Change from baseline in 24-hour mean plasma glucose based on 8-point self-monitored plasma glucose (SMPG) profiles 5- Change from baseline in variability of 24-hour mean plasma glucose based on 8-point SMPG profiles 6- Number (%) of patients with hypoglycemia 7- Number (%) of patients with hyperglycemia with ketosis 8- Number (%) of patients with adverse events |
1-Porcentaje de pacientes con valores de HbA1c <7,5% en el mes6 en general y sin ningún episodio de hipoglucemia sintomática severa y/o documentada (SMPG <54mg/dl; 3,0mmol/l) durante los últimos3meses delperiodo principalde aleatorización (desde la fecha de aleatorizaciónhasta el mes 6 (visita 14), independientemente dela interrupción del tratamiento del estudio); 2- Cambio desde el inicio en la glucosa plasmática en ayunas 3- Porcentaje de pacientes con GPA ?130 mg/dl (7,2 mmol/l) en el mes 6 en general y sin ningún episodio de hipoglucemia sintomática severa y/o documentada (SMPG ?54 mg/dl; 3,0 mmol/l) durante los últimos 3 meses del periodo principal de aleatorización de 6 meses; 4- Cambio en la glucosa plasmática media durante 24 horas basado en los perfiles de SMPG de 8 puntos desde la visita basal hasta el mes 6; 5- Cambio en la variabilidad de la glucosa plasmática media durante 24 horas basado en los perfiles de SMPG de 8 puntos desde la visita basal hasta el mes 6; 6- (%) de los pacientes con hipoglucemia 7- (%) de los pacientes con hiperglucemia en cetosis 8- (%) de pacientes con acontecimientos adversos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Week 26 2- Baseline; Week 26 3- Week 26 4- Baseline; Week 26 5- Baseline; Week 26 6- Up to Month 12 7- Up to Month 12 8- Up to Month 12 |
1- Semana 26 2- Basal; Semana 26 3- Semana 26 4- Basal; Semana 26 5- Basal; Semana 26 6- Hasta el mes 12 7- Hasta el mes 12 8- Hasta el mes 12 |
|
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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Brazil |
Canada |
Chile |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Latvia |
Mexico |
Poland |
Romania |
Russian Federation |
Spain |
United Kingdom |
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
|
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 |