E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 Diabetes Mellitus |
Diabetes Mellitus tipo 1 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 1 Diabetes Mellitus |
Diabetes Mellitus tipo 1 |
|
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 | 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 |
The purpose of this study is to determine if adding dapagliflozin to insulin is a safe and effective therapy to improve glycemic control in patients with type 1 diabetes |
El obejtivo de este estudio es determinar si la adición de dapagliflozina a insulina es un tratamiento seguro y efectivo para mejorar el control glucémico en pacientes con diabetes tipo 1. |
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E.2.2 | Secondary objectives of the trial |
- % change in total daily insulin dose and body weight. - Change in: - mean value of 24-hr glucose readings obtained from CGM - mean amplitude of glucose excursion of CGM 24-hr glucose readings - % CGM 24-hr glucose readings between > or = 70 and < or = 180 mg/dL - Proportion of subjects with A1C reduction > or = 0.5% and no severe hypoglycemia events. |
- % del cambio en la dosis total de insulina y peso corporal - Cambio en: - valor medio de glucosa obtenido por medición de MCG de 24h - amplitud media de las excursiones glucémicas por medición de MCG de 24h - % de lecturas de MCG de 24h entre ?70 y ?180 mg/dl -Proporción de sujetos con una reducción de A1C ?0,5% y ningún evento hipoglucémico severo |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Blood Sample Amendment 01 - Site Specific (original version, dated 10-Sep-14)
The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb is conducting this study on behalf of AstraZeneca. AstraZeneca is the sponsor for the MB102229 study and they will be responsible for the pharmacogenetic portion of this study including the logistically aspects related to this amendment. AstraZeneca will use DNA obtained from the blood sample and health information collected from the main clinical trial, MB102229, to study the association between genetic variation and drug response to Dapagliflozin in combination with insulin being used for the treatment of diabetes and also its susceptibility to Type 1 diabetes. AstraZeneca may also use the DNA to study the causes and further progression of Type 1 Diabetes and other Metabolic Diseases. Samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective. |
Enmienda Número 01 de fecha 10-Septiembre-2014 sobre las muestras de sangre para Farmacogenética: El objetivo de esta enmienda es permitir la recogida y almacenamiento de muestras de sangre para su uso en una futura investigación farmacogenética exploratoria. Bristol-Myers Squibb lleva a cabo este estudio en representación de AstraZeneca. AstraZeneca es el promotor del estudio MB 102-229 y será el responsable de la parte farmacogenética de este estudio, incluyendo los aspectos logísticos relacionados con esta enmienda. AstraZeneca usará ADN obtenido de muestras de sangre e información de salud recogida del ensayo clínico MB 102-229 para estudiar la asociación entre variaciones genéticas y la respuesta a dapagliflozina en combinación con insulina usada en el tratamiento de la diabetes y también su susceptibilidad a diabetes Tipo 1. AstraZeneca podría también usar el ADN para estudiar las causas y posterior progresión de la diabetes tipo 1 y otras enfermedades metabólicas. Las muestras de este estudio podrían usarse junto con resultados de investigación farmacogenética de otros estudios clínicos que compartan este objetivo |
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E.3 | Principal inclusion criteria |
1- Diagnosis of T1DM: Central laboratory test of C-peptide < 0.7 ng/ml 2- Insulin use for at least 12 months per patient reported or medical records and a- Method of insulin administration (MDI or CSII) must have been unchanged for at least 3 months prior to the screening visit. Subjects must be on a total insulin dose of >or= 0.3 U/kg/day for at least 3 months prior to the screening visit. b- If on MDI insulin administration, subject must be on >or= 3x injections per day. 3- A1C eligibility criteria include: Screening Visit: Central laboratory A1C >or= 7.7% and <or= 11.0% |
1- Diagnóstico de DMT1: Medición por laboratorio central del péptido C < 0,7 ng/ml 2- Uso de insulina durante al menos 12 meses según información del paciente o historial médico a- El método de administración de insulina (MID o ISCI) no debe haberse modificado al menos 3 meses antes de la visita de selección. Los sujetos deben estar a una dosis total de insulina de ?0,3 U/kg/día al menos 3 meses antes de la visita de selección b- Si la forma de administración de insulina es MID, debe ser ? 3 inyecciones por día. 3- Los criterios de eligibilidad de A1C incluyen: A1C por laboratorio central en la visita de selección: ?7,7% y ?11,0% |
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E.4 | Principal exclusion criteria |
- History of T2DM or maturity onset diabetes of young (MODY), pancreatic surgery, or chronic pancreatitis. - Previous use of dapagliflozin and/or any other SGLT-2 inhibitors - Use of metformin and/or thiazolidinediones within 2 months prior to the Screening visit - Any non-insulin, antihyperglycemic agent, within 1 month prior to the Screening visit - History of diabetes ketoacidosis (DKA) requiring medical intervention (eg, emergency room visit and/or hospitalization) within 1 month prior to the Screening visit - History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 1 month prior to the Screening visit - Frequent episodes of severe hypoglycemia as defined by more than one episode requiring medical assistance, emergency care (paramedics or emergency room care), and/or glucagon therapy administered by a third-party individual within 1 month prior to the Screening visit |
- Antecedentes de DMT2 o diabetes del adulto de inicio juvenil (MODY), cirugía pancreática o pancreatitis crónica - Uso previo de dapagliflozina y/o cualquier otro inhibidor de SGLT-2 - Uso de metformina y/o tiazolidindionas en los 2 meses previos a la visita de selección - Cualquier agente antihiperglucémico no insulínico durante el mes previo a la visita de selección - Antecedentes de cetoacidosis diabética (CAD) que requiera intervención médica (por ej., visita a urgencias y/o hospitalización) durante el mes previo a la visita de selección - Antecedentes de ingreso hospitalario para control glucémico (hiperglucemia o hipoglucemia) durante el mes previo a la visita de selección - Episodios frecuentes de hipoglucemia severa definida como más de un episodio que requiere asistencia médica, atención en urgencias (asistencia paramédica o en el servicio de urgencias) y/o tratamiento con glucagón administrado por otra persona durante el mes previo a la visita de selección. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The change in HbA1C from baseline at Week 24 |
Cambio en HbA1C desde inicio de tratamiento hasta semana 24. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to 24 weeks |
Desde inicio de tratamiento hasta semana 24. |
|
E.5.2 | Secondary end point(s) |
%change in total daily insulin dose and body weight
Change in: - mean value of 24-hr glucose readings obtained from CGM - mean amplitude of glucose excursion of CGM 24-hr glucose readings - % CGM 24-hr glucose readings between >or=70 and <or=180 mg/dL
Proportion of subjects with A1C reduction >0.5% and no severe hypoglycemia events. |
- % del cambio en la dosis total de insulina y peso corporal - Cambio en: - valor medio de glucosa obtenido por medición de MCG de 24h - amplitud media de las excursiones glucémicas por medición de MCG de 24h - % de lecturas de MCG de 24h entre ?70 y ?180 mg/dl - Proporción de sujetos con una reducción de A1C ?0,5% y ningún evento hipoglucémico severo |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to 24 weeks |
Desde inicio de tratamiento hasta semana 24. |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | No |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Australia |
Austria |
Belgium |
Canada |
Denmark |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Mexico |
Romania |
Spain |
Sweden |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |