Type 2 Diabetes Mellitus

為期 12 週的治療期間內，針對以飲食及運動無法適當控制血糖的第二型糖尿病受試者，評估 fasiglifam 25 mg 每日兩次及 fasiglifam 50 mg 每日一次對於血糖控制的療效。

錠劑

TAK-875

110

25 mg, 50 mg

•主要評估指標：糖化血色素在第 12 週相較於基準點的變化
•次要評估指標：空腹血糖值在第 12 週相較於基準點的變化

Inclusion Criteria
Subject eligibility is determined according to the following criteria:
1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. The subject is male or female and 18 years of age or older with a historical diagnosis of T2DM.
4. The subject has an HbA1c level ≥7.0% and ≤10.0% and FPG ≤270 mg/dL (15.0 mmol/L) at
Screening Visit.
5. The subject has been treated with diet and exercise but has not received treatment with
antidiabetic agents within 12 weeks prior to Screening Visit (Exception: if a subject has
received other antidiabetic therapy for ≤7 days in total within the 2 months prior to Screening Visit).
6. The subject has a body mass index (BMI) ≤45 kg/m2 at Screening.
7. Subjects regularly using other, nonexcluded medications, must be on a stable dose for at least 4 weeks prior to Screening Visit. However, as needed (PRN) use of prescription or
over-the-counter medications is allowed at the discretion of the investigator.
8. 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.
9. A female subject of childbearing potential* who is sexually active with a nonsterilized* male partner agrees to routinely use adequate contraception* from signing of the informed consent throughout the duration of the study and for 30 days after the last dose of study drug.

Exclusion Criteria
Any subject who meets any of the following criteria will not qualify for entry into the study:
1. The subject received any investigational compound within 30 days prior to Screening Visit or has received an investigational antidiabetic drug within the 3 months prior to Screening Visit.
2. The subject was randomized into a previous fasiglifam study. (Note: If the subject has been entered into the placebo run in phase or titration phase of another fasiglifam study, but has not been randomized into the double-blind treatment, then the subject could still be considered to be screened in this study.)
3. The subject is an immediate family member, study site employee, or is in a dependant
relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
4. The subject donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
5. The subject has a hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for
females at Screening.
6. The subject has a systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at
Screening (If the subject meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after the initial measurement and decision will be made based on the second measurement).
7. The subject has a history of cancer that has been in remission for <5 years prior to Screening. A history of basal cell carcinoma or stage 1 squamous cell carcinoma of the skin is allowed.
8. The subject has ALT and/or AST levels >2.0× upper limit of normal (ULN) at Screening.
9. The subject has a total bilirubin level greater than the ULN at Screening. Exception: if a subject has documented Gilbert’s syndrome the subject will be allowed with an elevated bilirubin level per the investigator’s discretion.
10. The subject has a serum creatinine ≥1.5 mg/dL (≥133μmol/L) (males) and ≥1.4 mg/dL
(≥124 μmol/L) (females) and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 at Screening.
11. The subject has uncontrolled thyroid disease as determined by the investigator.
12. The subject has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
13. The subject had gastric banding, or gastric bypass surgery within one year prior to Screening.
14. The subject has a known history of infection with human immunodeficiency virus (HIV),
hepatitis B virus, or hepatitis C virus.
15. The subject had coronary angioplasty, coronary stent placement, coronary bypass surgery, MI, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.
16. The subject has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of fasiglifam.
17. The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
18. The subject received excluded medications prior to Screening Visit or is expected to receive excluded medication as listed in Section 7.4, Excluded Medications and Treatments.
19. If female, the subject is pregnant (confirmed by laboratory testing, ie, serum/urine human chorionic gonadotropin (hCG), in females of childbearing potential) or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
20. The subject is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.
21. The subject has any other physical or psychiatric disease or condition that in the judgment of the investigator may affect life expectancy or may make it difficult to successfully manage and follow the subject according to the protocol.

Inclusion Criteria
Subject eligibility is determined according to the following criteria:
1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. The subject is male or female and 18 years of age or older with a historical diagnosis of T2DM.
4. The subject has an HbA1c level ≥7.0% and ≤10.0% and FPG ≤270 mg/dL (15.0 mmol/L) at
Screening Visit.
5. The subject has been treated with diet and exercise but has not received treatment with
antidiabetic agents within 12 weeks prior to Screening Visit (Exception: if a subject has
received other antidiabetic therapy for ≤7 days in total within the 2 months prior to Screening Visit).
6. The subject has a body mass index (BMI) ≤45 kg/m2 at Screening.
7. Subjects regularly using other, nonexcluded medications, must be on a stable dose for at least 4 weeks prior to Screening Visit. However, as needed (PRN) use of prescription or
over-the-counter medications is allowed at the discretion of the investigator.
8. 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.
9. A female subject of childbearing potential* who is sexually active with a nonsterilized* male partner agrees to routinely use adequate contraception* from signing of the informed consent throughout the duration of the study and for 30 days after the last dose of study drug.

Exclusion Criteria
Any subject who meets any of the following criteria will not qualify for entry into the study:
1. The subject received any investigational compound within 30 days prior to Screening Visit or has received an investigational antidiabetic drug within the 3 months prior to Screening Visit.
2. The subject was randomized into a previous fasiglifam study. (Note: If the subject has been entered into the placebo run in phase or titration phase of another fasiglifam study, but has not been randomized into the double-blind treatment, then the subject could still be considered to be screened in this study.)
3. The subject is an immediate family member, study site employee, or is in a dependant
relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
4. The subject donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
5. The subject has a hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for
females at Screening.
6. The subject has a systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at
Screening (If the subject meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after the initial measurement and decision will be made based on the second measurement).
7. The subject has a history of cancer that has been in remission for <5 years prior to Screening. A history of basal cell carcinoma or stage 1 squamous cell carcinoma of the skin is allowed.
8. The subject has ALT and/or AST levels >2.0× upper limit of normal (ULN) at Screening.
9. The subject has a total bilirubin level greater than the ULN at Screening. Exception: if a subject has documented Gilbert’s syndrome the subject will be allowed with an elevated bilirubin level per the investigator’s discretion.
10. The subject has a serum creatinine ≥1.5 mg/dL (≥133μmol/L) (males) and ≥1.4 mg/dL
(≥124 μmol/L) (females) and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 at Screening.
11. The subject has uncontrolled thyroid disease as determined by the investigator.
12. The subject has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
13. The subject had gastric banding, or gastric bypass surgery within one year prior to Screening.
14. The subject has a known history of infection with human immunodeficiency virus (HIV),
hepatitis B virus, or hepatitis C virus.
15. The subject had coronary angioplasty, coronary stent placement, coronary bypass surgery, MI, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.
16. The subject has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of fasiglifam.
17. The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
18. The subject received excluded medications prior to Screening Visit or is expected to receive excluded medication as listed in Section 7.4, Excluded Medications and Treatments.
19. If female, the subject is pregnant (confirmed by laboratory testing, ie, serum/urine human chorionic gonadotropin (hCG), in females of childbearing potential) or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
20. The subject is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.
21. The subject has any other physical or psychiatric disease or condition that in the judgment of the investigator may affect life expectancy or may make it difficult to successfully manage and follow the subject according to the protocol.