TAK-875 (Fasiglifam) in Combination With Sitagliptin in Adults With Type 2 Diabetes
Condition: Diabetes
MeSH terms: Diabetes Mellitus
Intervention: Placebo; TAK-875; TAK-875
Intervention description: TAK-875 placebo-matching tablets; TAK-875 tablets; TAK-875 tablets
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the effect of TAK-875 (fasiglifam) in combination
      with sitagliptin on glycemic control in adults with type 2 diabetes.
    

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 is male or female and aged 18 years or older with a historical
             diagnosis of T2DM.

          4. The participant meets one of the following criteria:

               -  The participant has an HbA1c between 7.5% and 10.5%, inclusive and has been
                  taking a stable dose of sitagliptin 100 mg for at least 8 weeks, with or without
                  metformin, prior to the Screening Visit. A participant who is taking metformin
                  must have received a stable daily dose (≥1500 mg or documented maximum tolerated
                  dose [MTD]) for at least 8 weeks before Screening. This participant will enter
                  the 2-week single-blind Placebo Run-In Period according to Study Schedule A, or;

               -  The participant has an HbA1c between 7.5% and 10.5%, inclusive and has been
                  taking any other DPP-IV inhibitor (with or without metformin) for at least 8
                  weeks prior to the Screening Visit. A participant who is taking metformin must
                  have received a stable daily dose (≥1500 mg or documented MTD) for at least 8
                  weeks before Screening. This participant will enter the 8-week Switching Period
                  according to Study Schedule B. Following this 8-week period, the participant must
                  qualify for all Inclusion/Exclusion Criteria prior to entering the 2-Week Placebo
                  Run-in Period by completing the Week ( 3) procedures including having an HbA1c
                  level between 7.5% and 10.5%.

             Note: An enrollment cap may be applied to ensure no more than approximately 20% of
             randomized participants are receiving a DPP-IV inhibitor without metformin at
             baseline.

          5. The participant has had no treatment with antidiabetic agents other than DPP-IV
             inhibitors and metformin within 2 months prior to Screening (Exception: if a
             participant has received other antidiabetic therapy for ≤7 consecutive days within the
             2 months prior to Screening).

          6. The participant has a body mass index (BMI) ≤45 kg/m2 at Screening.

          7. Participants 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 medication is allowed at the discretion of the investigator.

          8. A female participant 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.

          9. The participant is able and willing to monitor glucose with a home glucose monitor and
             consistently record his or her own blood glucose concentrations and complete
             participant diaries.

        Exclusion Criteria:

          1. Has received any investigational compound within 30 days prior to Screening or has
             received an investigational antidiabetic drug within 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; biological or legally adopted) or may consent under duress.

          4. 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 gm/L) for males and ≤10 g/dL (≤100 gm/L) for females
             at the Screening Visit.

          6. Has a systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at Screening
             (If the participant meets this exclusion criteria, the assessment may be repeated once
             at least 30 minutes after the initial measurement and a decision will be made based on
             the second measurement).

          7. Has history of cancer that has been in remission for <5 years prior to Screening.
             (Exception: A history of basal cell carcinoma or stage 1 squamous cell carcinoma of
             the skin is allowed.)

          8. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels
             >2.0x the upper limit of normal (ULN) at Screening.

          9. Has a total bilirubin level greater than the ULN at Screening. Exception: if a
             participant has documented Gilbert's Syndrome, they will be allowed with an elevated
             bilirubin level per the investigator's discretion.

         10. Has a serum creatinine ≥1.5 mg/dL (≥133 μmol/L) [males] and ≥1.4 mg/dL (≥124 μmol/L)
             [females] and/or estimated glomerular filtration rate (GFR) <60 mL/min/1.73m^2 at
             Screening.

         11. Has uncontrolled thyroid disease.

         12. Has a history of laser treatment for proliferative diabetic retinopathy within 6
             months prior to Screening.

         13. Has had gastric banding or gastric bypass surgery within one year prior to Screening.

         14. Has a known history of infection with human immunodeficiency virus (HIV), Hepatitis B
             virus (HBV), or Hepatitis C virus (HCV).

         15. 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
             3 months prior to or at Screening.

         16. Has a history of pancreatitis.

         17. Has a history of hypersensitivity, allergies or has had an anaphylactic reaction(s) to
             any component of TAK-875 as well as 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. Received excluded medications prior to the Screening Visit 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.