E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pediatric Patients with Type 2 Diabetes Mellitus Not Adequately Controlled with Metformin and/or Basal Insulin |
Pacientes pediátricos con diabetes mellitus tipo 2 no controlados adecuadamente con metformina y/o insulina basal |
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E.1.1.1 | Medical condition in easily understood language |
Pediatric Patients with Type 2 Diabetes Mellitus Not Adequately Controlled with Metformin and/or Basal Insulin |
Pacientes pediátricos con diabetes mellitus tipo 2 no controlados adecuadamente con metformina y/o insulina basal |
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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 | 19.0 |
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 |
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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 demonstrate safety of 14-day repeated lixisenatide doses with 3 ascending doses as compared to placebo in pediatric patients with T2DM. |
Demostrar la seguridad de dosis repetidas de lixisenatida de 5 μg, 10 μg y 20 µg durante 14 días en comparación con placebo en pacientes pediátricos con diabetes mellitus tipo 2 |
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E.2.2 | Secondary objectives of the trial |
-To evaluate plasma concentrations of lixisenatide after repeated doses (3 ascending doses) and pharmacokinetic parameters of repeated lixisenatide doses in pediatric patients with T2DM. -To evaluate the change from baseline in fasting and post-prandial plasma glucose concentrations during a standardized meal test after 3 ascending repeated doses of lixisenatide in comparison to placebo. |
-Evaluar las concentraciones plasmáticas de lixisenatida tras las dosis repetidas de 5 µg, 10 µg y 20 µg y los parámetros farmacocinéticos de las dosis repetidas de lixisenatida de 20 µg en pacientes pediátricos con DMT2 - Evaluar el cambio respecto al nivel basal en las concentraciones de glucosa plasmática en ayunas y posprandial durante una prueba de ingesta de alimentos estandarizada tras dosis repetidas de lixisenatida de 5 μg, 10 μg y 20 µg en comparación con placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male or female patients aged ≥10 and <18 years old (at least 4 patients below 16 years old). -Body mass index (BMI) >85th percentile for age and gender; BMI ≤50 kg/m^2. -Male and female patients with documented T2DM insufficiently controlled with metformin ≥1000 mg/day (or maximum tolerated dose according to the Investigator’s judgment) at a stable dose and regimen for 8 weeks prior to randomization and/or basal insulin at stable dose (±20%) and regimen for 8 weeks prior to randomization. -Glycated hemoglobin (HbA1c) >6.5% and ≤11% at screening. |
-Pacientes de sexo masculino o femenino de edad ≥10 y <18 años (como mínimo 4 pacientes menores de 16 años) -Índice de masa corporal (IMC) > percentil 85 por edad y sexo e IMC ≤50 kg/m2 -Pacientes de sexo masculino y femenino con DMT2 documentada no controlados adecuadamente con metformina ≥1000 mg/día (o la dosis máxima tolerada según el criterio del investigador) a una dosis y pauta estables durante las 8 semanas anteriores a la aleatorización y/o con insulina basal a una dosis (±20 %) y pauta estables durante las 8 semanas anteriores a la aleatorización - HbA1c superior a 6,5 % y inferior o igual a 11 % en la selección |
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E.4 | Principal exclusion criteria |
-If female, ongoing pregnancy (defined as positive serum pregnancy test), breast-feeding. -Sexually active postmenarchal female patient who does not agree to use an adequate and highly effective method of contraception throughout the study duration and according to local regulation (ie, hormonal contraception, condom, etc.). -Diabetes other than T2DM. -Fasting plasma glucose >250 mg/dL (>13.9 mmol/L) at screening. -Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin and basal insulin (eg, alpha glucosidase inhibitor, glucagon-like peptide [GLP-1] receptor agonist, dipeptidyl peptidase-IV [DPP-IV] inhibitors, short-acting insulin etc.) within 1 month prior to the screening visit. -History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease. |
-Si sexo femenino, embarazo en curso (que se define como positivo de la prueba de embarazo en suero), en periodo de lactancia. - Paciente postmenárquicas, sexualmente activa que no esté de acuerdo en utilizar un método anticonceptivo adecuado y altamente eficaz durante toda la duración del estudio y de acuerdo con las regulaciones locales (Es decir, los anticonceptivos hormonales, preservativos, etc.). -Diabetes distinta de la DMT2. -Glucosa plasmática en ayunas superior a 250 mg / dl (> 13,9 mmol / L) en la selección -Uso de otros antidiabéticos orales o inyectables o agentes hipoglucemiantes distintos de metformina e insulina basal (por ejemplo, alfa inhibidor de la glucosidasa, péptido similar al glucagón [GLP-1] agonista de los receptores, inhibidores de la dipeptidil peptidasa-IV [DPP-IV] inhibidores, de acción corta insulina, etc.) dentro de 1 mes antes de la visita de selección. -Historia de pancreatitis inexplicable, pancreatitis crónica, pancreatectomía, cirugía de estómago / gástrico, enfermedad inflamatoria del intestino. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Number of patients with adverse events (AEs) - Number of patients with treatment-emergent adverse events (TEAEs) - Number of patients with anti-lixisenatide antibodies |
- Número de pacientes con eventos adversos (AA) - Número de pacientes con eventos adversos emergentes del tratamiento (TEAEs) - Número de pacientes con anticuerpos anti-lixisenatide |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 10 weeks |
Hasta 10 semanas |
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E.5.2 | Secondary end point(s) |
1 : - Assessment of PK parameters: lixisenatide plasma concentration - Assessment of pharmacodynamic parameters: plasma glucose AUC-0-4.5 hours, FPG, 1H-PPG excursion and 2H-PPG excursion
2 : - Assessment of PK parameters: maximum concentration (Cmax) - Assessment of PK parameters: time to reach Cmax (Tmax) - Assessment of PK parameters: area under up to last concentration (AUClast) - Assessment of PK parameters: area under curve (AUC) |
1: - Evaluación de los parámetros farmacocinéticos: concentración plasmática lixisenatide - Evaluación de los parámetros farmacodinámicos: glucosa en plasma AUC-0-4,5 horas, FPG, 1H-PPG excursión y excursión 2H-PPG
2: - Evaluación de los parámetros farmacocinéticos: concentración máxima (Cmax) - Evaluación de los parámetros farmacocinéticos: tiempo para alcanzar la Cmax (Tmax) - Evaluación de los parámetros farmacocinéticos: área bajo hasta última concentración (AUCfinal) - Evaluación de los parámetros farmacocinéticos: área bajo la curva (AUC) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 : Day 14, Day 28 and Day 42 2 : Day 42 |
1: Día 14, Día 28 y el Día 42 2: Día 42 |
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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 | No |
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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
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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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LVLS |
Última visita del último paciente |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |