Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ertugliflozin 5 mg; Ertugliflozin 15 mg; Placebo for ertugliflozin 5 mg; Metformin; Sitagliptin; Glimepiride; Insulin; Placebo for ertugliflozin 10 mg
Intervention description: Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks; Ertugliflozin, oral, 5 mg and 10 mg tablet once daily for 52 weeks; Matching placebo for ertugliflozin 5 mg, oral, once daily for 52 weeks; Participants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period.; Participants are to remain on their stable doses of sitagliptin (oral, 100 mg once daily) while receiving blinded investigational product during the double-blind treatment period.; Glimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion; Insulin glargine rescue medication, injectable, as required. In the event that an investigator considers use of glimepiride to not be appropriate for a participant meeting protocol specified glycemic rescue criteria, insulin glargine can be initiated as the rescue medication, and managed by the investigator according to clinical practice guidelines of the local country.; Matching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Glimepiride; Ertugliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 464.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a safety and efficacy study of ertugliflozin (MK-8835/PF-04971729) in the treatment
      of participants with type 2 diabetes mellitus who have inadequate glycemic control on
      metformin and sitagliptin. The primary objective of the trial is to assess the hemoglobin A1C
      (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo
      with an underlying hypothesis that addition of treatment with ertugliflozin provides greater
      reduction in A1C compared with the addition of placebo; the primary objective will be tested
      for both 5-mg and 15-mg doses of ertugliflozin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of type 2 diabetes mellitus (T2DM)

          -  On stable diabetes therapy of metformin with either sitagliptin or another dipeptidyl
             peptidase-4 (DPP-4) inhibitor or a sulfonylurea (SU) prior to study participation and
             is willing to wash-off/switch from another DPP-4 inhibitor/SU to sitagliptin

          -  Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2

          -  Male, postmenopausal female or surgically sterile female

          -  If a female of reproductive potential, agrees to remain abstinent or to use (or have
             their partner use) 2 acceptable combinations of birth control while participating in
             the trial and for 14 days after the last use of study drug

        Exclusion Criteria:

          -  History of type 1 diabetes mellitus or a history of ketoacidosis

          -  History of other specific types of diabetes (e.g., genetic syndromes, secondary
             pancreatic diabetes, diabetes due to endocrine disorders, drug- or chemical-induced,
             and post-organ transplant)

          -  A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2)
             or DPP-4 inhibitor

          -  On a weight-loss program or weight-loss medication or other medication associated with
             weight changes and is not weight stable

          -  Has undergone bariatric surgery within the past 12 months or >12 months and is not
             weight stable

          -  Has been treated with insulin (except for short-term use [<= 7 days]), injectable
             antihyperglycemic agents (AHAs) (e.g., pramlintide, exenatide, liraglutide),
             pioglitazone or rosiglitazone, other sodium-glucose co-transporter 2 (SGLT2)
             inhibitors, alpha glucosidase inhibitors or meglitinides, bromocriptine (Cycloset™),
             colesevelam (Welchol™), or any other non-protocol approved AHAs within 12 weeks of
             study participation

          -  Has active, obstructive uropathy or indwelling urinary catheter

          -  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 participation

          -  A history of malignancy ≤5 years prior to study participation, except for adequately
             treated basal or squamous cell skin cancer or in situ cervical cancer

          -  Known history of Human Immunodeficiency Virus (HIV)

          -  Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or
             any other clinically significant hematological disorder (such as aplastic anemia,
             myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

          -  A medical history of active liver disease (other than nonalcoholic hepatic steatosis),
             including chronic active hepatitis B or C, primary biliary cirrhosis, or active
             symptomatic gallbladder disease

          -  Has any clinically significant malabsorption condition

          -  If taking thyroid replacement therapy, has not been on a stable dose for at least 6
             weeks prior to study participation

          -  Has been previously randomized in a study with ertugliflozin

          -  Has participated in other studies involving an investigational drug within 30 days
             prior or during study participation

          -  Has undergone a surgical procedure within 6 weeks prior to or planned major surgery
             during study participation

          -  Has a positive urine pregnancy test

          -  Is pregnant or breast-feeding, or is planning to conceive during the trial, including
             14 days following the last dose of study medication

          -  Planning to undergo hormonal therapy in preparation to donate eggs during the trial,
             including 14 days following the last dose of study medication

          -  Excessive consumption of alcoholic beverages or binge drinking

          -  Has donated blood or blood products within 6 weeks of study participation or plans to
             donate blood or blood products at any time during the trial