E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus |
Diabete Mellito di tipo II |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes mellitus |
Diabete Mellito di tipo II |
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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 | 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 |
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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 the non-inferiority of H0E901-U300 to Lantus, in change of glycated hemoglobin A1c (HbA1c) |
Dimostrare la non inferiorità di HOE901-U300 rispetto a Lantus per quanto riguarda la variazione dei livelli di emoglobina glicata A1c (HbA1c) |
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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 |
Dimostrare la superiorità di HOE901-U300 rispetto a Lantus in relazione a: - Percentuale di pazienti con almeno un evento ipoglicemico grave e/o confermato (mediante glucosio plasmatico ≤70 mg/dl [3,9 mmol/L]) dalle 22:00 alle 08:59 del mattino successivo - Percentuale di pazienti con almeno un evento ipoglicemico notturno (dalle 00:00 alle 05:59) grave e/o confermato (≤70 mg/dl [3,9 mmol/L]) - Percentuale di pazienti con almeno un evento ipoglicemico grave e/o confermato (mediante glucosio plasmatico ≤70 mg/dl [3,9 mmol/L]) in qualsiasi momento del giorno - Variazioni dei valori HbA1c
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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. |
- Pazienti di età ≥ 65 anni con diabete mellito di tipo 2, non adeguatamente controllato, in regime farmacologico antidiabetico senza insulina o con insulina basale come unica insulina - Consenso informato firmato
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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]). |
- Livelli di HbA1c alla visita di screening: - < 7,0% o > 10,0% nei pazienti che assumono insulina basale - < 7,5% o > 11,0% nei pazienti naïve all'insulina - Storia di diabete mellito di tipo 2 almeno un 1 anno prima dello screening - Pazienti con dosaggio non stabile di insulina basale (±10% nelle ultime 8 settimane prima della visita di screening) - Variazione del dosaggio del trattamento antidiabetico non insulinico o inizio di un nuovo farmaco per la riduzione della glicemia nelle ultime 8 settimane prima dello screening - Uso cronico (> 10 giorni di uso continuo nei 6 mesi precedenti) di iniezioni di bolo di insulina, mediante somministrazione separata o in combinazione con insulina basale, per esempio insulina premiscelata. Per i pazienti naïve all'insulina: uso attuale o pregresso di insulina, eccetto che in caso di uso per un massimo di 10 giorni consecutivi (per esempio malattia acuta, intervento chirurgico), durante l'anno precedente lo screening - Disordini cognitivi e demenza valutati clinicamente e mediante punteggio Mini– Mental State Examination (MMSE) <24 o qualsiasi disordine neurologico che potrebbe verosimilmente influire sulla capacità del paziente di seguire le procedure dello studio. Il paziente sarà eleggibile nonostante un punteggio MMSE <24 se lo sperimentatore stabilisse che il punteggio basso riflette il livello educativo e culturale e non la demenza, sempre che il paziente sia in grado di soddisfare i requisiti dello studio - Pazienti con malattia renale in stadio terminale (<15 ml/min/1,73m2, per misurazione della velocità di filtrazione glomerulare stimata (eGFR) mediante la Modification of Diet in Renal Disease [MDRD]).
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c from baseline |
Variazioni dei livelli di HbA1c |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline, week 26 |
baseline, settimana 26 |
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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) Incidenza (% di pazienti) di eventi ipoglicemici (sintomatico o asintomatico) gravi e/o confermati (mediante glucosio plasmatico ≤70 mg/dl [3,9 mmol/L]) dalle 22:00 alle 08:59 del mattino successivo 2) Incidenza (% di pazienti) di ipoglicemie notturne (dalle 00:00 alle 05:59) grave e/o confermata (≤ 70 mg/dl [3,9 mmol/L]) (sintomatica o asintomatica) 3) Incidenza (% di pazienti) di ipoglicemie (sintomatica o asintomatica) gravi e/o confermate (mediante glucosio plasmatico ≤70 mg/dl [3,9 mmol/L]) in qualsiasi momento del giorno 4) Percentuale di pazienti con HbA1c (a) < 7,5% (b) <7,0% 5) Percentuale di pazienti con HbA1c (a) < 7,5% (b) <7,0% alla settimana 26, senza eventi ipoglicemici gravi e/o confermati (mediante glucosio plasmatico≤70 mg/dl [3,9 mmol/L]) durante le 26 settimane di trattamento 6) Variazione della FPG dal basale alla settimana 26 7) Variazione del punteggio dei questionari PRO dal basale alla settimana 26 8) Percentuale di pazienti che necessitano di terapia “rescue” durante le 26 settimane di trattamento
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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 – 8: settimana 26 6 – 7: baseline, settimana 26
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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 | 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 | 5 |
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 |
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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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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 | 7 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 15 |