| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type 2 diabete mellitus |
| Diabete mellito di tipo 2 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Type 2 diabete mellitus |
| Diabete mellito di tipo 2 |
|
| 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 |
|
| 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 objective of the study is to investigate the efficacy, safety and tolerability of BI 10773 25 mg/linagliptin 5 mg FDC qd and of BI 10773 10 mg/ linagliptin 5 mg FDC qd compared to the individual components (BI 10773 25 mg, BI 10773 10 mg, and linagliptin 5 mg) given for 52 weeks in treatment naïve and metformin treated patients with type 2 diabetes mellitus with insufficient glycaemic control. |
| Obiettivo dello studio e' valutare efficacia, sicurezza e tollerabilita' delle due combinazioni a dosaggio fisso: BI 10773 25 mg+linagliptin 5 mg qd e BI 10773 10 mg+ linagliptin 5 mg qd , confronto alle componenti singole (ovvero al BI 10773 25 mg, al BI 10773 10 mg e a linagliptin 5 mg) in 52 settimane di trattamento in pazienti con diabete mellito di tipo 2 o non trattati od in trattamento con metformina, con insufficiente controllo glicemico |
|
| E.2.2 | Secondary objectives of the trial |
| 1. Change from baseline in fasting plasma glucose 2. Change from baseline in body weight |
| Gli endpoint secondari principali sono: la variazione dal basale del glucosio nel plasma a digiuno (FPG) dopo 24 settimane di trattamento e la variazione dal basale nel peso corporeo dopo 24 settimane di trattamento. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Diagnosis of type 2 diabetes mellitus prior to informed consent 2. Male and female patients on diet and exercise regimen who are drug-naive (defined as absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomization) or pre-treated with metformin (>=1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label)unchanged for 12 weeks prior to randomisation. 3. HbA1c >= 7.0% and <= 10.5% (>= 53.0 mmol/mol and <= 91.3 mmol/mol) at Visit 1 (screening) 4. Age >= 18 years 5. Body Mass Index (BMI) <=45 kg/m2 at Visit 1 (screening) 6. Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation |
| 1.Diagnosi di diabete mellito di tipo 2 prima della firma del consenso informato (CI) 2.Pazienti maschi e femmine con regime dietetico e di esercizio fisico sia non sottoposti a trattamento (definito come assenza di terapia antidiabetica orale, analoghi GLP-1 o insulina per 12 settimane prima della randomizzazione) sia pre-trattati con metformina (>=1500 mg/dì o alla dose massima tollerata o secondo AIC con terapia immodificata per le 12 settimane prima della randomizzazione. 3.HbA1c >= 7.0% e <= 10.5% (>= 53.0 mmol/mol e <= 91.3 mmol/mol) alla visita 1 (screening) 4.Eta' >= 18 years 5.Body Mass Index (BMI) <=45 kg/m2 alla visita 1 (screening) 6.Consenso informato scritto firmato e datato entro la data della visita 1 in accordo con le GCP e Legislazione Nazionale. |
|
| E.4 | Principal exclusion criteria |
| 1. Uncontrolled hyperglycemia 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. Any other antidiabetic drug within 12 weeks prior to randomization (except metformin background therapy as defined via inclusion criterion 2) Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent 4. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in period 5. Impaired renal function, defined as eGFR <60 ml/min (MDRD formula) as determined during screening and/or run-in period 6. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption 7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years 8. Blood dyscrasias or any disorders causing hemolysis or unstable (shortened half-life) red blood cell (e.g. malaria, babesiosis, hemolytic anemia) 9. Contraindications to metformin according to the local label 10. Treatment with anti-obesity drugs within 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight 11. Current treatment with systemic steroids (other than inhalative steriods) at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM 12. Pre-menopausal women (last menstruation <=1 year prior to informed consent) who: - are nursing or pregnant or - are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, complete sexual abstinence (if acceptable by local health authorities), double barrier method and vasectomized partner 13. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to trial procedures or trial drug intake, in the judgment of the investigator 14. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participation in the follow-up period of another trial (partipation in observational studies is permitted) 15. Any other clinical condition that, in the opinion of the investigator, would jeopardize patient's safety while participating in this clinical trial |
| 1.Iperglicemia incontrollata a livelli di glucosio >240 mg/dl (>13.3 mmol/L) dopo digiuno notturno durante la fase di run-in con placebo e confermata da una seconda misurazione (non nel medesimo giorno). 2.Qualunque altro farmaco antidiabetico preso nelle 12 settimane prima della randomizzaione (eccetto metformina come terapia di background come definito nel criterio di inclusione 2) 3.Sindrome coronarica acuta (non-STEMI, STEMI e angina pectoris instabile), ictus o TIA entro 3 mesi prima del consenso informato 4.Indicazione di disfunzione epatica definita come livelli serici di ALT (SGPT), AST (SGOT), o fosfatasi alcalina oltre 3 volte il limite superiore di normalità (ULN) determinato durante lo screening e/o il run-in 5.Disfunzione renale definita come eGFR <60 ml/min (MDRD formula) determinata durante lo screening e/o il run-in 6.Chirurgia per il controllo ponderale entro i due anni precedenti ed altri interventi gastrointestinali che inducono malassorbimento cronico 7.Storia medica di cancro (eccetto carcinoma delle cellule basali) e/o trattamento per cancro negli ultimi 5 anni 8.Discrasie od altri disturbi che causano emolisi e emivita breve/instabile degli eritrociti (e.g. malaria, babesiosi, anemia emolitica) 9.Controindicazioni alla metformina in accordo all'AIC 10.Trattamento con farmaco anti obesità entro 3 mesi prima della firma del CI o qualunque altro trattamento al momento dello screening (i.e. chirurgia, regime dietetico aggressivo, etc.) che porti ad instabilita' ponderale 11.Trattamento corrente con steroidi sistemici (tranne gli inalatori) al momento della firma del CI o modifiche di dosaggio negli ormoni tiroidei entro le 6 settimane precedenti la firma del CI o qualunque altro disturbo endocrino tranne il T2DM 12.Donne in pre-menopausa (ultima mestruazione <=1 anno prima del CI) che: - siano in allattamento o in gravidanza - siano in eta' fertile e non usino un metodo contraccettivo accettabile dal punto di vista medico o che non intendano usarlo per tutta la durata dello studio e che non accettino di effettuare periodicamente un test di gravidanza durante lo studio. Metodi accettabili di contraccezione includono: legamento delle tube, patch transdermico, dispositivi intrauterini (IUDs/IUSs), contraccettivi orali, impiantabili o iniettabili, astinenza sessuale completa (se accettabile dalle Autorità Sanitarie Nazionali), metodo a doppia barriera e partner vasectomizzato. 13.Abuso di alcol o sostanze stupefacenti entro i 3 mesi prima della firma del CI che possa interferire con la partecipazione allo studio o qualunque condizione presente che possa abbassare la compliance del paziente alle procedure dello studio o all'assunzione del farmaco, a giudizio dello sperimentatore. 14.Assunzione di un farmaco sperimentale in altro studio clinico entro 30 giorni dalla prima assunzione di farmaco per il presente studio o partecipazione al periodo di follow-up di un altro studio clinico (studi osservazionali sono permessi) 15.Qualunque altra condizione medica che, a giudizio dello sperimentatore metterebbe a rischio la sicurezza del paziente mentre partecipa allo studio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in HbA1c |
| L'endpoint primario e' la variazione dal basale della emoglobina glicata (HbA1c) dopo 24 settimane di trattamento. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| After 24 weeks of treatment |
| dopo 24 settimane di trattamento. |
|
| E.5.2 | Secondary end point(s) |
| 1. Change from baseline in fasting plasma glucose 2. Change from baseline in body weight |
| Gli endpoint secondari principali sono: la variazione dal basale del glucosio nel plasma a digiuno (FPG) dopo 24 settimane di trattamento e la variazione dal basale nel peso corporeo dopo 24 settimane di trattamento. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| After 24 weeks of treatment |
| dopo 24 settimane di trattamento. |
|
| 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 | 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 42 |
| 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 |
| India |
| Korea, Republic of |
| Lebanon |
| Malaysia |
| Mexico |
| Peru |
| Philippines |
| Russian Federation |
| Taiwan |
| 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
|
|
| 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 | 25 |
| 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 | 25 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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