E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus (T2DM) |
Diabete Mellito di tipo 2 (T2DM) |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063624 |
E.1.2 | Term | Type II diabetes mellitus inadequate control |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012613 |
E.1.2 | Term | Diabetes mellitus non-insulin-dependent |
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 evaluate the efficacy of TAK-875 plus metformin compared to placebo plus metformin and sitagliptin plus metformin on glycemic control as measured by change from baseline in HbA1c over a 24-week Treatment Period. |
Valutare l’efficacia di TAK-875 più metformina rispetto al placebo più metformina e sitagliptin più metformina sul controllo glicemico, misurato in base al cambiamento dal basale in HbA1c durante un periodo di trattamento di 24 settimane. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of TAK-875 plus metformin compared to placebo plus metformin and sitagliptin plus metformin on other measures of glycemic control, including clinically meaningful levels of response in HbA1c and fasting plasma glucose (FPG) over a 24-week Treatment Period. |
Valutare l’effetto di TAK-875 più metformina rispetto al placebo più metformina e sitagliptin più metformina su altre misure di controllo glicemico, inclusi i livelli clinicamente significativi di risposta in HbA1c e glicemia plasmatica a digiuno (fasting plasma glucose, FPG) durante un periodo di trattamento di 24 settimane. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria: 1. The subject is male or female and 18 years of age or older with a historical diagnosis of T2DM. 2. The subject meets one of the following criteria: – The subject has an HbA1c level ≥7.5 and <10.5%, and has been on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose [MTD]) of metformin for at least 2 months prior to Screening. This subject will immediately enter the Placebo Run-in Period according to Study Schedule A, or; – The subject has an HbA1c level ≥7.5 and <10.5%, and has been on a stable daily dose of <1500 mg of metformin without documented MTD for at least 2 months prior to Screening. After completing the Screening Visit, this subject will have their metformin dose immediately increased to ≥1500 mg (or MTD) for an 8-week Titration Period according to Study Schedule B. Following this 8-week period, the subject must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures including having an HbA1c level ≥7.5 and <10.5%. 3. The subject has had no treatment with antidiabetic agents other than metformin within 2 months prior to Screening (Exception: if a subject has received other antidiabetic therapy for ≤7 days within the 2 months prior to Screening). 4. The subject has a body mass index (BMI) ≤45 kg/m² at Screening. 5. Subjects regularly using other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. However, PRN (as needed) use of prescription or over-the counter medications is allowed at the discretion of the investigator. 6. The subject is able and willing to monitor glucose with a home glucose monitor and consistently record his or her own blood glucose concentrations and complete subject diaries. |
•Soggetti di sesso maschile o femminile, di almeno 18 anni di età, con un’anamnesi di T2DM. •Il soggetto soddisfa uno dei seguenti criteri:–il soggetto presenta un livello HbA1c ≥ 7,5% e < 10,5% e ha ricevuto una dose stabile di ≥ 1500 mg (o dose tollerata massima documentata [maximum tolerated dose, MTD]) di metformina per almeno 2 mesi prima dello screening. Tale soggetto entrerà immediatamente nel periodo run-in con placebo in base al Programma A dello studio, oppure;–il soggetto presenta un livello HbA1c ≥ 7,5% e < 10,5% e ha ricevuto una dose stabile di < 1500 mg di metformina, senza MTD documentata, per almeno 2 mesi prima dello screening. Dopo il completamento della visita di screening, la dose di metformina del soggetto sarà aumentata fino a ≥ 1500 mg (o MTD) per un periodo di titolazione di 8 settimane, in base al Programma B dello studio. Dopo questo periodo di 8 settimane, l’idoneità del soggetto alla partecipazione dovrà essere stabilita nel periodo run-in con placebo completando le procedure della Settimana-3, incluso il riscontro di un livello HbA1c ≥ 7,5% e < 10,5%. •Il soggetto non è stato sottoposto a trattamento con agenti antidiabetici diversi da metformina nel corso dei 2 mesi antecedenti allo screening (eccezione: un soggetto che abbia ricevuto altra terapia antidiabetica per ≤ 7 giorni entro i 2 mesi precedenti allo screening). •Il soggetto presenta un indice di massa corporea (Body Mass Index, BMI) al momento dello screening di ≤ 45 kg/m².• I soggetti che assumono regolarmente altri farmaci non esclusi, devono aver ricevuto una dose stabile per almeno 4 settimane prima dello screening. Comunque, all’occorrenza, l’utilizzo di farmaci su prescrizione o da banco è consentito a discrezione dello sperimentatore.•Il soggetto è in grado e disposto a controllare a casa il glucosio tramite il monitor di glucosio e, di conseguenza, a registrare le proprie concentrazioni di glucosio nel sangue e a completare i diari del soggetto. |
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E.4 | Principal exclusion criteria |
1. The subject donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study. 2. Hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening Visit. 3. The subject has systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at Screening Visit. (If the subject meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after the initial measurement.) 4. The subject has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening. 5. The subject has had treatment for gastric banding or gastric bypass surgery within one year prior to Screening. 6. The subject had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening. 7. The subject has a history of pancreatitis. |
•Il soggetto ha donato o ricevuto prodotti emoderivati entro le 12 settimane antecedenti allo screening o intende donare sangue nel corso dello studio.•Emoglobina di ≤ 12 g/dl (≤ 120 g/l) per gli uomini e di ≤ 10 g/dl (≤ 100 g/l) per le donne al momento della visita di screening.•Il soggetto presenta una pressione sanguigna sistolica di ≥ 160 mm Hg o una pressione diastolica di ≥ 95 mm Hg al momento della visita di screening. (Se il soggetto soddisfa questo criterio di esclusione, la valutazione può essere ripetuta una volta almeno 30 minuti dopo la misurazione iniziale.) •Il soggetto è stato sottoposto in passato a trattamento laser per retinopatia diabetica proliferativa 6 mesi prima dello screening.•Il soggetto è stato sottoposto a trattamento per bendaggio gastrico o a intervento chirurgico di bypass gastrico entro un anno dallo screening. •Il soggetto è stato sottoposto o ha sofferto di angioplastica coronarica, impianto di stent coronarico, intervento chirurgico di bypass coronarico, infarto miocardico, angina pectoris instabile,elettrocardiogramma anomalo significativo, incidente cerebrovascolare o attacco ischemico transitorio nei 3 mesi precedenti lo screening o allo momento dello stesso. •Il soggetto presenta un’anamnesi di pancreatite. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c at Week 24. |
•Variazione rispetto al basale in HbA1c alla Settimana 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 24 of treatment. |
Settimana 24 di trattamento. |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints: - Incidence of HbA1c <7% at Week 24. - Change from baseline in FPG at Week 24. |
Gli endpoint secondari per questo studio sono: •Incidenza di HbA1c < 7% alla Settimana 24. •Variazione rispetto al basale in FPG alla Settimana 24. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 24 of treatment |
Settimana 24 di trattamento. |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | 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 | 4 |
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 | 67 |
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 |
Croatia |
Korea, Democratic People's Republic of |
Malaysia |
Thailand |
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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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 | 36 |
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 | 45 |
E.8.9.2 | In all countries concerned by the trial days | 0 |