12-Week Study of DS-8500a in Subjects With Type 2 Diabetes Mellitus on Metformin
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin 100 mg; DS-8500a 25mg; Placebo Tablet; Placebo Capsule
Intervention description: Two sitagliptin 50 mg tablets, over-encapsulated to provide a once-daily dose of 100 mg, for oral administration; DS-8500a 25mg tablet for oral administration; Placebo matching DS-8500a tablet for oral administration; Placebo matching sitagliptin over-capsule for oral administration
Intervention MeSH terms: Sitagliptin Phosphate; Firuglipel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 298.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: type 2 diabetes mellitus; interventional; double blind; phase 2

Summary:

      The hypothesis of this Phase 2, 12-week study, is that DS-8500a will improve glycemic control
      relative to placebo, based on changes in HbA1c, with acceptable safety and tolerability, in
      patients with Type 2 Diabetes Mellitus (T2DM) who are treated with metformin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to provide written informed consent and adhere to the study visit schedule and
             treatment

          -  Diagnosed with Type 2 diabetes mellitus as defined in the American Diabetes
             Association Standards of Medical Care in Diabetes 2015

          -  Male or female ≥ 18 and ≤ 70 years of age

          -  Screening fasting C-peptide > 0.5 ng/mL

          -  Women of child bearing potential (WOCBP) must be willing to use double-barrier
             contraception for the entire study

          -  WOCBP must have a negative pregnancy test (human chorionic gonadotropin, beta subunit
             [βhCG]) before entering the Lead-in Period

          -  Body mass index ≥ 25 kg/m2 and ≤ 45 kg/m2 at the Screening Visit

          -  On stable (≥ 8 weeks) metformin monotherapy ≥ 1000 mg/day

          -  Screening HbA1c ≥ 7.0% and ≤ 10%

          -  Taking ≥ 80% and ≤ 120% of both dispensed DS-8500a placebo tablets and sitagliptin
             placebo capsules during the Lead-in Period

        Exclusion Criteria:

          -  History of type 1 diabetes and/or history of ketoacidosis

          -  History of insulin use for > 2 weeks within 2 months prior to the Screening Visit

          -  Two or more readings of fasting Self-monitoring of Blood Glucose (SMBG) > 240 mg/dL or
             worsening symptoms of hyperglycemia with one SMBG level of > 240 mg/dL during the
             second week of Lead-in Period, confirmed by laboratory measurement

          -  Screening hemoglobin <12 g/dL for males and <11 g/dL for females

          -  Blood donation within 2 months prior to the Screening Visit or plans to donate blood
             or blood products during the study

          -  Subjects after bariatric surgery or any gastric bypass

          -  Screening thyroid stimulating hormone (TSH) levels not within normal range (based on
             reference laboratory values )

          -  Screening Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 2.0 x
             upper limit of normal (ULN), and/or total bilirubin > 1.5 x ULN. If a subject has
             total bilirubin > 1.5 ULN, unconjugated and conjugated bilirubin fractions should be
             analyzed and only subjects documented to have Gilbert's syndrome may be enrolled

          -  Screening Serum creatinine ≥ 1.5 mg/dL for males and ≥ 1.4 mg/dL for females, or
             creatinine clearance (CrCl) < 50 mL/min for both males and females

          -  Screening Creatine kinase (CK) > 3.0 × ULN

          -  History of unstable angina, myocardial infarction, cerebrovascular accident, transient
             ischemic attack, peripheral arterial event or any revascularization procedure during
             the 6 months prior to the Screening Visit or planned vascular procedures or surgery
             during study period

          -  History of congestive heart failure (CHF)

          -  Exclusionary concomitant medications:

             a. Eight weeks prior to screening and throughout the duration of the study:

          -  Any diabetes medication other than metformin; any prescription or over the counter
             medication for weight-loss.

          -  Systemic corticosteroids (including nasal and inhaled), with the exception of use of
             topical and ophthalmic corticosteroids.

          -  Rosuvastatin > 20 mg daily. b. During treatment periods, additional medications will
             be prohibited based on potential drug-drug interaction (DDI) (see Section 5.6)

          -  Subjects with anticipated interruption in metformin or study drug use during the
             course of the clinical trial (e.g., due to an imaging procedure involving iodinated
             contrast media)

          -  Subjects in whom treatment with sitagliptin 100 mg is contraindicated ( e.g., known
             hypersensitivity or intolerance to sitagliptin) or may not be medically advisable
             (e.g., history of pancreatitis)

          -  Abuse of or dependence on prescription medications, illicit drugs, or alcohol within
             the last 1 year

          -  Any history of a malignancy other than basal cell carcinoma within the past 5 years

          -  Pregnancy or breast-feeding, or intent to become pregnant during the study period

          -  Known (or evidence of) infection with human immunodeficiency virus

          -  Any condition, laboratory abnormality, or concomitant therapy which, in the opinion of
             the Investigator, might pose a risk to the subject or make participation not in the
             subject's best interest

          -  Subject is currently enrolled in or has not yet completed at least 30 days since
             ending another investigational device or drug study or is receiving other
             investigational agents

          -  A direct or familial relationship with the Sponsor, Investigator, or site personnel
             affiliated with the study