Ertugliflozin and Sitagliptin Co-administration Factorial Study (VERTIS FACTORAL, MK-8835-005)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Matching Placebo to Ertugliflozin 5 mg; Matching Placebo to Ertugliflozin 10 mg; Matching Placebo to sitagliptin 100 mg; Ertugliflozin 5 mg; Ertugliflozin 10 mg; Sitagliptin 100 mg; Metformin >= 1500 mg/day; Insulin Glargine Rescue Medication; Glimepiride Rescue Medication
Intervention description: Placebo to ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period; Placebo to ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period; Placebo to sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period; Ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period; Ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period; Sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period; Metformin >= 1500 mg/day, tablets, oral, for 52 weeks while receiving blinded investigational product during the double-blind treatment period; Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion; Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion
Intervention MeSH terms: Metformin; Insulin Glargine; Sitagliptin Phosphate; Glimepiride; Ertugliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1233.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study of co-administration of ertugliflozin (MK-8835/PF-04971729) and sitagliptin
      given together or alone along with metformin in participants with Type 2 diabetes mellitus
      (T2DM) and inadequate glycemic control on metformin monotherapy. The primary hypothesis of
      this study is that ertugliflozin 15 mg daily plus sitagliptin 100 mg daily provides greater
      hemoglobin A1C (A1C)-lowering compared with sitagliptin 100 mg daily alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes mellitus as per American Diabetes Association guidelines

          -  On metformin monotherapy (>=1500 mg/day) for >=8 weeks with a Visit 1/Screening A1C
             >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy
             (>=1500 mg/day) for <8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58
             mmol/mol and <=97 mmol/mol) OR On metformin monotherapy <1500 mg/day with a Visit
             1/Screening A1C >=8.0% and <=11.5% (>=64 mmol/mol and <=102 mmol/mol)

          -  Body mass index (BMI) >=18.0 kg/m^2

          -  Male or female not of reproductive potential

          -  Female of reproductive potential who agrees to remain abstinent from heterosexual
             activity or to use 2 acceptable combinations of contraception

        Exclusion Criteria:

          -  History of type 1 diabetes mellitus or ketoacidosis

          -  History of other specific types of diabetes (e.g., genetic syndromes, secondary
             pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and
             post-organ transplant

          -  A known hypersensitivity or intolerance to any sodium glucose co-transporter 2 (SGLT2)
             inhibitor or sitagliptin

          -  Has been treated with any of the following agents within 12 weeks of study start or
             during the pre-randomization period: Insulin of any type (except for short-term use
             [i.e., <=7 days] during concomitant illness or other stress), other injectable
             anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), pioglitazone or
             rosiglitazone, other SGLT2 inhibitors, alpha glucosidase inhibitors or meglitinides,
             dipeptidyl-peptidase 4 inhibitor (DPP-4 inhibitor), sulfonylureas (SUs), bromocriptine
             (Cycloset™), colesevelam (Welchol™), any other antihyperglycemic agents (AHA) with the
             exception of the protocol-approved agents

          -  Is on a weight-loss program or weight-loss medication or other medication associated
             with weight changes and is not weight stable prior to study start

          -  Has undergone bariatric surgery within the past 12 months or >12 months and is not
             weight stable prior to study start

          -  A history of myocardial infarction, unstable angina, arterial revascularization,
             stroke, transient ischemic attack, or New York Heart Association (NYHA) functional
             class III-IV heart failure within 3 months of study start

          -  Active, obstructive uropathy or indwelling urinary catheter

          -  History of malignancy <=5 years prior to study start, except for adequately treated
             basal cell or squamous cell skin cancer or in situ cervical cancer

          -  A known history of human immunodeficiency virus (HIV)

          -  A blood dyscrasia or any disorder causing hemolysis or unstable red blood cells, or a
             clinically important hematological disorder (e.g. aplastic anemia, myeloproliferative
             or myelodysplastic syndromes, thrombocytopenia)

          -  A medical history of active liver disease (other than non-alcoholic hepatic
             steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or
             symptomatic gallbladder disease

          -  Any clinically significant malabsorption condition

          -  Current treatment for hyperthyroidism

          -  On thyroid replacement therapy and not on a stable dose for at least 6 weeks prior
             study start

          -  On a previous clinical study with ertugliflozin

          -  Estimated glomerular filtration rate (eGFR) (using the 4-variable Modification of Diet
             in Renal Disease Study Equation (MDRD) equation) <60 mL/min/1.73 m^2

          -  Serum creatinine >= 1.3 mg/dL (115 µmol/L) for males and >= 1.2 mg/dL (106 µmol/L) for
             females

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times upper
             limit of normal

          -  Hemoglobin <12 g/dL (120 g/L) for males and <11 g/dL (110 g/L) for females.

          -  Participated in other studies involving investigational drug(s) 30 days prior to study
             start

          -  Surgical procedure within 6 weeks prior to study start or major surgery planned during
             the trial

          -  Positive urine pregnancy test

          -  Pregnant or breast-feeding, or planning to conceive during the trial, including 14
             days following the last dose of study medication

          -  Planning to undergo hormonal therapy in preparation for egg donation during the trial,
             including 14 days following the last dose of study medication

          -  Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or
             engages in binge drinking

          -  Donated blood or blood products within 6 weeks of study start