12-Week Study of DS-8500a in Subjects With Type 2 Diabetes Mellitus on Metformin

A Randomized, Double-Blind, Placebo-Controlled With Active Comparator, 12-Week Study of DS-8500a in Subjects With Type 2 Diabetes Mellitus on Metformin

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.

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