E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type 2 diabetes. |
Pazienti affetti da diabete di tipo 2 |
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E.1.1.1 | Medical condition in easily understood language |
Patients with type 2 diabetes. |
Pazienti affetti da diabete di tipo 2 |
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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 | 14.0 |
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 | 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 main objective of this study is to identify the dose of linagliptin (BI1356) in paediatric patients. |
L'obiettivo principale dello studio e' quello di identificare la dose di linagliptin in pazienti pediatrici. |
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E.2.2 | Secondary objectives of the trial |
The study will also investigate the pharmacokinetics (PK), the pharmacodynamics (PD) and the PK/PD relationship, efficacy and safety of linagliptin in the paediatric population. |
lo studio esaminera' la farmacocinetica (PK)/farmacodinamica (PD), l'efficacia e la sicurezza di linagliptin nella popolazione pediatrica. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Paediatric patients (children and adolescents), aged 10 to 17 years at the time of screening (i.e. Visit 1A) 2.Documented diagnosis of type 2 diabetes mellitus at least 3 months prior to randomisation (i.e. Visit 2) 3.Insufficient glycaemic control (i.e. an HbA1c > 7.0% and <= 10.0%) at screening (i.e. Visit 1A) despite treatment with diet and exercise alone 4.Negative for islet cell antigen (ICA) auto-antibodies and glutamic acid decarboxylase (GAD) auto-antibodies at Visit 2 5.C-peptide levels (serum) >= 1.5 ng/ml (at 90 min following a Boost challenge) at Visit 2 6.Compliance during the open-label placebo run-in period between 75% and 125%. 7.Written informed consent provided by the patient's parent(s) (or legal guardian) and assent by the patient at the latest by the date of Visit 1A in accordance with GCP and local legislation. Informed assent will be sought according to the patient's age, level of maturity, competence and capacity. All informed consent/assent forms will be consistent with ICH-GCP and local IEC/IRB requirements. |
1.Pazienti pediatrici (bambini e adolescenti), di eta' compresa tra i 10 e i 17 anni al momento dello screening (cioe' Visita 1A). 2.Diagnosi documentata di diabete mellito di tipo 2 almeno 3 mesi prima della randomizzazione (cioe' Visita 2). 3.Insufficiente controllo glicemico (cioe' una HbA1c > 7.0% and <= 10.0%) al momento dello screening (cioe' Visita 1A) nonostante trattamento con dieta e esercizio fisico. 4.Negativita' per gli auto-anticorpi anti-isole cellulari pancreatiche (ICA) e per gli auto-anticorpi anti-acido glutammico decarbossilasi (GAD). 5.Livelli di peptide C (sierici) >= 1.5 ng/ml (a 90 minuti dopo il Boost challenge) alla Visita 2. 6.Compliance durante il periodo di run-in con il placebo in aperto tra il 75% e il 125%. 7.Consenso informato scritto fornito dal genitore (i) (o tutore legale) e assenso da parte del paziente almeno alla data della Visita 1A in accordo con la GCP e la legislazione locale. L'assenso informato deve essere richiesto in base all'eta' del paziente, livello di maturita', competenza e capacita'. Tutti i moduli di consenso/ assenso dovranno essere stesi in accordo alle ICH-GCP e ai requiesiti dei Comitati Etici locali. |
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E.4 | Principal exclusion criteria |
1.Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (> 13.3 mmol/l) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day) 2.History of acute metabolic decompensation, such as diabetic ketoacidosis, within 3 months of screening (i.e. Visit 1A) 3.Current insulin therapy, or having received insulin for > 4 weeks within the 3 months prior to randomisation (i.e. Visit 2) 4. Treatment with weight reduction medications (including anti-obesity treatments) within 3 months prior to randomisation (i.e. the date of Visit 2) 5. Chronic treatment – treatment duration of more than two weeks - with medication known to affect glucose metabolism (e.g. metformin or systemic corticosteroids) within 3 months prior to randomisation (i.e. Visit 2) 6. Anticipated need for treatment with PGP (P-glycoprotein) and CYP 3A4 inhibitors or inducers during the placebo run-in period (Visit 1B onwards) and randomised period (Visits 2-6) of the study 7. Clinically significant renal disease (defined as estimated Glomerular Filtration Rate [eGFR] < 60 ml/min, i.e. moderate and severe renal impairment, calculated according to the Schwarz formula) as determined at screening 8. Clinically significant hepatic disease (defined as persistent serum levels of ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN)) as determined at screening 9. Gastrointestinal disorders that might interfere with study drug absorption 10.Patients presenting a secondary obesity as part of a syndrome (e.g. : Prader-Willi syndrome) 11.Female patients who are nursing or are pregnant 12. Female patients who have reached menarche (i.e. ANY vaginal bleeding, however scant or irregular) with a positive pregnancy test or who are sexually active and not using a medically accepted contraceptive method. 13. Patients with a history of belonephobia (needle phobia) in this age group 14. Patients with anaemia defined as shown below and as determined at screening(Visit 1A): -children aged up to 12: haemoglobin of < 11.5 g/dl and haematocrit <35% -females aged > 12 or who reached menarche before this age: haemoglobin of < 12 g/dl and haematocrit < 36% -males aged > 12: haemoglobin of < 13 g/dl and haematocrit < 39%. 15. Active alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation according to the Investigator opinion. 16. Patients whose parent(s) (or legal guardian) will be unable to support the reporting of adverse event information (e.g. not fluent in an appropriate language, or no access to a telephone). 17. Patients whose home circumstances will mean they are unable to store the study rescue medication (insulin) appropriately. 18. Known hypersensitivity or allergy to the investigational product or its excipients or placebo 19. Participation in another trial with an investigational drug within 2 months prior to informed consent 20. Patients considered unreliable by the Investigator concerning the requirements for follow-up during the study and/or compliance with study medication administration 21. Any disease or clinically significant abnormality/clinical condition that may increase the risk associated with study participation or affect the study outcome, and in the judgement of the Investigator would make the patient inappropriate for entry into the study. |
1.Iperglicemia non controllata con livelli di glucosio > 240 mg/dl (> 13.3 mmol/l) dopo una notte a digiuno durante il periodo di run-in con placebo e confermata da una seconda misurazione (non nello stesso giorno). 2.Storia di decompensazione metabolica acuta, come ketoacidosi diabetica entro 3 mesi dallo screening. 3.Terapia corrente con insulina, o aver assunto insulina per piu' di 4 settimane entro 3 mesi prima della randomizzazione. 4.Trattamento con farmaci per la riduzione del peso (incluso trattamenti anti-obesita') entro 3 mesi prima della randomizzazione. 5.Trattamento cronico - trattamento con durata superiore alle 2 settimane - con farmaci noti per influenzare il metabolismo del glucosio (ad esempio metformina o corticosteroidi sistemici) entro 3 mesi prima della randomizzazione. 6.Bisogno anticipato per il trattamento con inibitori o induttori della PGP (glicoproteina P) e del CYP 3A4 durante il periodo di run-in con il placebo e nel periodo di randomizzazione dello studio. 7.Malattia renale clinicamente significativa (definita come stima della velocita' di filtrazione glomerulare [eGFR] <60 ml/min, cioe', moderata e grave insufficienza renale, calcolata secondo la formula di Schwarz) stabilita allo screening. 8.Malattia epatica clinicamente significativa (definita come livelli sierici persistenti di ALT (SGPT), AST (SGOT), o fosfatasi alcalina superiori a 3 volte il limite superiore della normalita' (ULN)), stabilita allo screening. 9.Disturbi gastrointestinali che potrebbero interferire con l'assorbimento del farmaco sperimentale. 10.Pazienti che presentano una obesita' secondaria come parte di una sindrome (ad esempio: Sindrome di Prader-Willi). 11.Pazienti femmine in allattamento o gravidanza. 12.Le pazienti femmine che hanno raggiunto il menarca (cioe' QUALSIASI sanguinamento vaginale, anche se scarso o irregolare) con un test di gravidanza positivo o che sono sessualmente attive e non stanno usando un metodo contraccettivo clinicamente accettato. 13.Pazienti con una storia di belonefobia in questa fascia di eta'. 14.Pazienti con anemia definita, come illustrato di seguito, stabilita allo screening: -I bambini sino a 12 anni: emoglobina < 11.5 g/dl e ematocrito < 35%; - Donne di eta' > 12 anni o che hanno raggiunto il menarca prima di questa eta': emoglobina < 12 g/dl e ematocrito < 36%; - Maschi di eta' > 12 anni: emoglobina < 13 g/dl e ematocrito < 39%. 15.Abuso attivo di alcol o droghe nei 3 mesi precedenti al consenso informato che potrebbero interferire con la partecipazione allo studio in accordo con la decisione dello Sperimentatore. 16.Pazienti i cui genitore(i)(o tutore legale) non saranno in grado di supportare la comunicazione di informazioni sugli eventi avversi. 17.Pazienti che per il loro contesto abitativo non saranno in grado di conservare il farmaco di salvataggio (insulina) in maniera adeguata. 18.Nota ipersensibilita' o allergia al prodotto in sperimentazione o dei suoi eccipienti o placebo. 19.Partecipazione a un altro studio clinico con un farmaco sperimentale entro 2 mesi prima del consenso informato. 20. Pazienti considerati inaffidabili dal ricercatore in merito ai requisiti per il follow-up durante lo studio e/o per l’aderenza con la somministrazione di farmaco in studio. 21.Qualsiasi anomalia o malattia clinicamente significativa / condizione clinica che puo' aumentare il rischio connesso con la partecipazione allo studio o puo' influenzare l'esito di studio, e che in base algiudizio dello Sperimentatore dovrebbe rendere il paziente inadeguato per l'ingresso nello studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this trial is the change from baseline in HbA1c (%) after 12 weeks of treatment. |
La variabile primaria di efficacia e' il cambiamento dal basale del valore di HbA1c dopo 12 settimane. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 12 weeks of treatment |
dopo 12 settimane |
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E.5.2 | Secondary end point(s) |
The study will also investigate the pharmacokinetics (PK), the pharmacodynamics (PD) and the PK/PD relationship, efficacy and safety of linagliptin in the paediatric |
lo studio esaminera' la farmacocinetica (PK)/farmacodinamica (PD), l'efficacia e la sicurezza di linagliptin nella popolazione pediatrica. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
dopo 12 settimane |
after 12 weeks of treatment |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Canada |
Korea, Republic of |
Mexico |
Peru |
Russian Federation |
United States |
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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
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For all patients completing the 12 week treatment period according to the protocol, a followup Visit 7 (clinic visit) should be performed at the end of the follow-up period of 7 days. |
LPLV inclusa una visita di follow-up 7 giorni dopo l'ultima visita per i pazienti che hanno completato 12 settimane di trattamento |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 27 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 30 |
E.8.9.2 | In all countries concerned by the trial days | 0 |