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 | 16.1 |
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 | 16.1 |
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 | 16.1 |
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 | 16.1 |
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 | 16.1 |
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 |
The primary objective is to demonstrate that no excess risk of CV composite events exists following treatment with
TAK-875 compared with placebo when given in combination with Standard of Care in subjects with T2DM and clinically evident CV disease or multiple risk factors for CV events. For purposes of this study, the primary MACE composite comprises CV death, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization for unstable angina (with or without revascularization). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate time from randomization to secondary MACE composite: CV death, nonfatal MI, and nonfatal stroke. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main Criteria for Inclusion:
1. Subjects who are 18 years of age or older;
2. Have a diagnosis of T2DM with an HbA1c between 7.0% and 10.5%, inclusive;
3. Subjects must have documentation of one of 3 High Risk factors (documented history of myocardial infarction, documented symptomatic peripheral arterial disease, or documented cerebrovascular disease), or have one of 5 Intermediate Risk factors (stable angina, multi vessel coronary disease, history of percutaneous coronary intervention, or specific clinical criteria with or without diabetic nephropathy);
4. Stable baseline ALT or AST levels;
5. Subject is able and willing to monitor glucose with a home glucose monitor and consistently record blood glucose concentrations in diaries;
6. If female of childbearing potential and sexually active with a non-sterilized male partner, agrees to use adequate contraception
throughout duration of the study and for 30 days after last dose of study medication. |
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E.4 | Principal exclusion criteria |
Main Criteria for Exclusion:
1. Subjects who have received any investigational medication within 30 days prior to Screening or any investigational
antidiabetic medication or excluded medications within 3 months prior to Screening;
2. Have been randomized into a previous TAK-875 study;
3. Are an immediate family member, study site employee, or are in a dependant relationship with a study site employee involved in the conduct of this study;
4. Are diagnosed with type 1 diabetes mellitus or latent
autoimmune diabetes in adults;
5. Hemodynamically unstable, including severe heart failure (New York Heart Association Class IV);
6. Hospitalized at Screening Visit for the cardiovascular inclusion event;
7. Have an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) level >3.0x upper limit of normal (ULN);
8. Have a total bilirubin level >ULN at screening;
9. Have an estimated glomerular filtration rate (eGFR) ≤15 mL/min/1.73m2 based on Modification of Diet in Renal Disease (MDRD) calculation and is currently on dialysis or expected to start dialysis within the next 6 months;
10. Have uncontrolled thyroid disease;
11. Have a known history of infection with human
immunodeficiency virus (HIV);
12. Have a known active infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) requiring antiviral treatment;
13. Have a history of drug or alcohol abuse within the 2 years prior to Screening;
14. Have a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to TAK-875;
15. Have a history of cancer that has been in remission for <5 years prior to Screening, with the exception of basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin;
16. If female, is pregnant or lactating or intending to become pregnant or donate ova throughout the study period and within 1 month after. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is the time from randomization to the first occurrences of any event in the primary
MACE composite (CV death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina, with or without
revascularization). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint for evaluation of primary endpoint will depend on when any of the events in the primary MACE composite will occur. |
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E.5.2 | Secondary end point(s) |
Secondary endpoint for this study is the time from randomization to the first occurrence of any event in the secondary MACE composite (CV death, nonfatal MI, nonfatal stroke). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint for evaluation of secondary endpoint will depend on when any of the events in the secondary MACE composite will occur. |
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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 | 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) | No |
E.8.2.2 | Placebo | Yes |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 152 |
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 |
Bulgaria |
Canada |
China |
France |
Italy |
Croatia |
New Zealand |
Romania |
Slovakia |
Argentina |
Australia |
Brazil |
Czech Republic |
Estonia |
Germany |
Guatemala |
Hong Kong |
Hungary |
Korea, Republic of |
Latvia |
Lithuania |
Malaysia |
Thailand |
Israel |
Mexico |
Peru |
Philippines |
Poland |
Russian Federation |
South Africa |
Taiwan |
Ukraine |
United Kingdom |
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 26 |