Clinical trial NCT01414920 (phase 2, status: completed)
Conditions: diabetes mellitus, type 2
ICD codes: E11.65, E11.9, E11.21, E11.36, E11.41, E11.42, E11.44
Drugs: placebo, tak-875, tak-875, sitagliptin, tak-875 and sitagliptin, tak-875 and sitagliptin
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, N[C@@H](CC(=O)N1CCN2C(C1)=NN=C2C(F)(F)F)CC1=CC(F)=C(F)C=C1F, N[C@@H](CC(=O)N1CCN2C(C1)=NN=C2C(F)(F)F)CC1=CC(F)=C(F)C=C1F, N[C@@H](CC(=O)N1CCN2C(C1)=NN=C2C(F)(F)F)CC1=CC(F)=C(F)C=C1F
Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          2. The participant or, when applicable, the participant'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 participant has either:

               -  A historical diagnosis of Type 2 Diabetes (T2DM) without the chronic use (defined
                  as >7 days) of anti-diabetic therapy within 8 weeks prior to Screening, and with
                  at least an 8-week documented history of a diet and exercise plan at Screening
                  OR,

               -  A historical diagnosis of T2DM and stable on at least 1500 mg per day (or maximum
                  tolerated dose) of metformin as monotherapy for at least 8 weeks at Screening.
                  Participants on a stable dose of metformin who enter the study will continue on
                  the same dose of metformin throughout the duration of the study.

          4. The participant is a man or woman and aged 18 to 80 years, inclusive.

          5. The participant's body mass index (BMI) (kg/m2) at Screening is ≥23 and ≤45.

          6. The participant has an glycosylated hemoglobin (HbA1c) level at Screening between 7.5%
             and 10.0%, inclusive, if on metformin and between 7.5% to 10.9%, inclusive, if treated
             with diet and exercise alone.

          7. The participant has a fasting plasma glucose level <14.4 mmol/L (<260 mg/dL), at
             Screening.

          8. The participant has a fasting C-peptide concentration ≥0.26 nmol/L (≥0.8 ng/mL) at
             Screening.

          9. If the participant takes any chronic, non-excluded medications, the dose of these
             medications must have been stable (no change in dose or drug) for at least 4 weeks
             prior to Screening.

         10. The participant is able and willing to monitor their glucose levels with a home
             glucose monitor and consistently record his or her own blood glucose concentrations
             according to the given instructions.

         11. A male participant who is nonsterilized and sexually active with a female partner of
             childbearing potential agrees to use adequate contraception from signing of informed
             consent throughout the duration of the study and for 30 days after last dose.

         12. A female participant of childbearing potential who is sexually active with a
             nonsterilized male partner agrees to use routinely adequate contraception from signing
             of informed consent throughout the duration of the study.

         13. A female participant of childbearing potential must have a negative serum human
             chorionic gonadotropin (HCG) pregnancy test at Screening (Visit 1) and at Placebo
             Run-in (Visit 2). A negative urine HCG pregnancy test is also required at
             Randomization (Visit 3), prior to administration of the first dose of double-blind
             study medication.

         14. The participant's compliance with single-blind study medication during the run-in
             phase is at least 80% and does not exceed 120% based on tablet counts performed by the
             study staff.

        Exclusion Criteria:

          1. The participant has received any investigational compound within 4 weeks prior to
             Screening.

          2. The participant has been enrolled in a previous TAK-875 study.

          3. The participant is an immediate family member, study site employee, or is in a
             dependent 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 participant has a history of hypersensitivity or allergies to TAK-875 or
             sitagliptin, or their excipients.

          5. The participant has a history of drug abuse (defined as any illicit drug use) or a
             history of alcohol abuse within 2 years prior to the Screening visit.

          6. The participant 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).

          7. The participant has systolic blood pressure ≥150 mm Hg or diastolic pressure ≥90 mm Hg
             at Screening (Visit 1) or Baseline (Visit 3) (as confirmed by repeat measurement 30
             minutes after initial measurement).

          8. The participant has a creatine phosphokinase (CPK) level ≥5x the upper limit of normal
             (ULN) at Screening.

          9. The participant has a hemoglobin level of ≤12 g/dL (120 gm/L) for men and ≤10 g/dL
             (100 gm/L) for women at Screening.

         10. The participant has ALT and/or AST levels ≥2.5x ULN at Screening.

         11. The participant has a total bilirubin level > ULN at Screening.

         12. The participant has a serum triglyceride concentration ≥4.5 mmol/L (≥400 mg/dL) at
             Screening.

         13. The participant has an estimated glomerular filtration rate ≤60mL/min using the
             Modification of Diet in Renal Disease (MDRD) equation at Screening.

         14. The participant has a documented history or concurrent signs of uncontrolled (not
             euthyroid) thyroid disease (eg, autoimmune thyroid diseases such as Graves disease and
             Hashimoto thyroiditis or active thyroid nodules).

         15. The participant has a history of pancreatitis.

         16. The participant has a history of laser treatment for proliferative diabetic
             retinopathy within 6 months prior to Screening.

         17. The participant has a history of gastric bypass surgery or has diabetic gastroparesis
             that in the investigator's opinion is moderate or severe and hence may impair
             absorption of study medication.

         18. The participant has had coronary angioplasty, coronary stent placement, coronary
             bypass surgery, myocardial infarction, unstable angina pectoris, clinically
             significant abnormal electrocardiogram (ECG), cerebrovascular accident or transient
             ischemic attack within 6 months prior or at Screening.

         19. The participant has a history of any hemoglobinopathy that may affect determination of
             HbA1c.

         20. The participant has a positive test result for hepatitis B surface antigen and
             antibody to hepatitis C virus, and/or has known history of human immunodeficiency
             virus at Screening.

         21. The participant has donated or received any blood products within 12 weeks prior to
             Screening.

         22. The participant received medication prior to Screening as listed in the excluded
             Medications section.

         23. If female, the participant is pregnant or lactating or intending to become pregnant
             before, during, or within 1 month after participating in this study; or intending to
             donate an ova during such time period.

         24. If male, the participant intends to donate sperm during the course of this study or
             for 30 days thereafter.

         25. The participant 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 participant according to the protocol.