Comparison of TAK-875 (Fasiglifam) With Placebo in Participants With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Placebo; Fasiglifam
Intervention description: Fasiglifam placebo-matching tablets; Fasiglifam 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: 421.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to determine the efficacy and safety of TAK-875 (fasiglifam),
      once daily (QD), in participants with type 2 diabetes mellitus (T2DM).
    

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 18 years of age or older with a historical
             diagnosis of T2DM.

          4. The participant has been treated with only diet and exercise for at least 12 weeks
             prior to Screening and has an HbA1c concentration between 7.0 % and 10.5%, inclusive,
             at Screening.

          5. The participant has received ≤7 days of any antidiabetic agent within 12 weeks prior
             to Screening.

          6. The participant 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
             for at least 4 weeks prior to Screening. However, as needed (PRN) use of prescription
             or over-the-counter medication is allowed at the discretion of the investigator.

          8. 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.

          9. A female participant of childbearing potential who is sexually active with a
             nonsterilized male partner agrees to use routinely 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.

        Additional Inclusion Criteria prior to Randomization

          1. The participant has an HbA1c concentration between 7.0 and 10.5%, inclusive, and a
             fasting plasma glucose (FPG) ≤270 mg/dL (≤15.0 mmol/L) at Week -1 Visit. (If the
             participant does not qualify for randomization based on these criteria, the
             assessments may be repeated weekly, for a maximum of 2 additional weeks).

          2. The participant's overall compliance with single-blind study medication during the
             Placebo Run-in Period is at least 75% and does not exceed 125% based on tablet counts
             performed by the study staff.

          3. A female participant of childbearing potential must have a negative urine hCG
             pregnancy test at Baseline (Visit 4) prior to Randomization and prior to
             administration of the first dose of double-blind study medication

        Exclusion Criteria:

          1. The participant 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. The participant has been randomized 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 (e.g., spouse, parent, child, or sibling; biological or legally adopted) or may
             consent under duress.

          4. The participant donated or received any blood products within 12 weeks prior to
             Screening or is planning to donate blood during the study.

          5. The participant has a hemoglobin ≤12 g/dL (≤120 gm/L) for males and ≤10 g/dL (≤100
             gm/L) for females at Screening.

          6. The participant has a systolic blood pressure ≥160 mm Hg or diastolic blood pressure
             ≥95 mm Hg at Screening (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 based on the second measurement).

          7. 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.

          8. The participant has an alanine aminotransferase (ALT) and/or aspartate
             aminotransferase (AST) levels >2.0x the upper limit of normal (ULN) at Screening.

          9. The participant has a total bilirubin level greater than the 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. The participant 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. The participant has uncontrolled thyroid disease.

         12. The participant has a history of laser treatment for proliferative diabetic
             retinopathy within 6 months prior to Screening.

         13. The participant has had gastric banding or gastric bypass surgery within one year
             prior to Screening.

         14. The participant has a known history of infection with human immunodeficiency virus
             (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).

         15. The participant 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 or at Screening.

         16. The participant has a history of hypersensitivity, allergies, or has had an
             anaphylactic reaction(s) to any component of TAK-875.

         17. The participant 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 participant received excluded medications prior to Screening or is expected to
             receive excluded medication.

         19. If female, the participant is pregnant (confirmed by laboratory testing, i.e., serum
             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 participant 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 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.

        Additional Exclusion Criteria prior to Randomization

          1. The participant received excluded medications during the Placebo Run-in Period.
             (Topical and inhaled corticosteroids are allowed).

          2. The participant has a systolic blood pressure ≥160 mm Hg or diastolic blood pressure
             ≥95 mm Hg at Baseline (Visit 4) (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 based on the second measurement).