E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus (T2DM) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029505 |
E.1.2 | Term | Non-insulin-dependent 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 | 14.1 |
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 | 14.1 |
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. |
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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. |
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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 type 2 diabetes mellitus-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 8 weeks 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 8 weeks 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. |
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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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint:
Change from baseline in HbA1c at Week 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
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 | 29 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 120 |
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 |
Bulgaria |
Czech Republic |
Hungary |
Italy |
Korea, Republic of |
Malaysia |
Slovakia |
Thailand |
United States |
Croatia |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 3 |