Comparison of Fasiglifam (TAK-875) With Sitagliptin When Used in Combination With Metformin in Patients With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Fasiglifam (TAK-875); Fasiglifam (TAK-875) Placebo; Sitagliptin; Sitagliptin Placebo; Metformin
Intervention description: Fasiglifam (TAK-875) tablets; Fasiglifam (TAK-875) placebo-matching tablets; Sitagliptin tablets; Sitagliptin placebo-matching tablets; Metformin tablets
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the efficacy of fasiglifam (TAK-875) plus metformin
      compared with sitagliptin plus metformin on glycemic control over a 24-week Treatment Period.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator, 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. Is male or female and 18 years of age or older with a historical diagnosis of type 2
             diabetes mellitus (T2DM).

          4. Meets one of the following criteria:.

               1. Has an HbA1c ≥8% 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 participant will immediately enter the Placebo Run-in Period
                  according to Study Schedule A, or;

               2. Has an HbA1c ≥8% 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, these participants will have their metformin dose
                  immediately increased to ≥1500 mg (or MTD) for an 8- to 12-week
                  Titration/Stabilization Period according to Study Schedule B. Following stable
                  administration of metformin ≥1500 mg (or MTD) for 8 weeks, the participant must
                  qualify for entry into the Placebo Run-in Period by completing the Week -3
                  procedures and have an HbA1c ≥8% and <10.5%.

          5. Has had no treatment with anti-diabetic agents other than metformin within 8 weeks
             prior to Screening (Exception: if a participant has received other anti-diabetic
             therapy for ≤7 days within the 8 weeks prior to Screening).

          6. Has a body mass index (BMI) ≤45 kg/m^2 at Screening.

          7. Participants regularly using other, non-excluded medications must be on a stable dose
             and regimen for at least 4 weeks prior to Screening. However, as needed use of
             prescription or over-the-counter medications is allowed at the discretion of the
             investigator. Note: Participants who require initiation of a chronically administered
             medication(s) due to a disease or condition diagnosed at Screening must be rescreened
             after the new regimen has been stabilized.

          8. A female participant of childbearing potential who is sexually active with a
             non-sterilized 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.

          9. Is able and willing to monitor glucose with a sponsor-provided home glucose monitor
             and consistently record his or her own blood glucose concentrations in diaries.

        Exclusion Criteria:

          1. Has received any investigational compound within 30 days prior to Screening or has
             received an investigational anti-diabetic drug within the 3 months prior to Screening.

          2. Has been randomized into a previous TAK-875 study.

          3. 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, or sibling) or may consent under duress.

          4. Has donated or received any blood products within 12 weeks prior to Screening or is
             planning to donate blood during the study.

          5. Has a hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at
             Screening.

          6. Has systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥95 mm Hg at
             Screening Visit. (If the participant meets this exclusion criterion, the assessment
             may be repeated once at least 30 minutes after the initial measurement and decision
             will be made on the second measurement.)

          7. Has history of cancer that has been in remission for <5 years prior to Screening. A
             history of basal cell carcinoma or stage I squamous cell carcinoma of the skin is
             allowed.

          8. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2 x
             upper limit of normal (ULN) at Screening.

          9. Has a total bilirubin level >ULN at Screening. Exception: if a participant has
             documented Gilbert's Syndrome the participant will be allowed with an elevated
             bilirubin level per the investigator's discretion.

         10. Has serum creatinine ≥1.5mg/dL (≥133μmol/L) if male or ≥1.4 mg/dL (≥124 μmol/L) if
             female and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2 at
             Screening.

         11. Has uncontrolled thyroid disease as determined by the investigator.

         12. Has a history of laser treatment for proliferative diabetic retinopathy within 6
             months prior to Screening.

         13. Has a history of pancreatitis.

         14. Has a history of gastric banding or gastric bypass surgery within one year prior to
             Screening.

         15. Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B
             virus (HBV), or hepatitis C virus (HCV).

         16. Had coronary angioplasty, coronary stent placement, coronary bypass surgery,
             myocardial infarction (MI), unstable angina pectoris, clinically significant abnormal
             electrocardiogram (ECG), cerebrovascular accident or transient ischemic attack within
             3 months prior to or at Screening.

         17. Has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s)
             to any component of TAK-875, metformin, or sitagliptin.

         18. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol
             abuse within 2 years prior to Screening.

         19. Has received excluded medications prior to Screening or is expected to receive
             excluded medications.

         20. If female, 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.

         21. Is unable to understand verbal or written English or any other language for which a
             certified translation of the approved informed consent is available.

         22. 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.