A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ertugliflozin 5 mg; Placebo 5 mg; Ertugliflozin 10 mg; Placebo 10 mg
Intervention description: Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks; Placebo to ertugliflozin, oral, tablet, 5 mg tablet once daily for 52 weeks; Ertugliflozin, oral, tablet, 10 mg tablet once daily for 52 weeks; Placebo to ertugliflozin, oral, tablet, 10 mg tablet once daily for 52 weeks
Intervention MeSH terms: Ertugliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 468.0
Sex: All
Minimum age: 25 Years
Healthy volunteers: No

Summary:

      This study will evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in
      participants with Type 2 diabetes mellitus with Stage 3 Chronic Kidney Disease (CKD) who have
      inadequate glycemic control on background antihyperglycemic therapy. The duration of this
      trial will be up to 67 weeks. This study will consist of a 1-week Screening Period, a 10-week
      wash-off period from metformin, if needed, and a 2-week placebo run-in period, a 52-week
      double-blind treatment period, and a 14-day post-treatment follow-up period. The primary
      objective of this 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 to
      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 in accordance with American Diabetes Association
             guidelines

          -  Have Stage 3 chronic kidney disease

          -  On stable diabetes therapy (diet/exercise therapy alone or anti-hyperglycemic agents
             [AHA] monotherapy or combination therapy) for at least 6 weeks prior to study
             participation OR on metformin (with or without diet/exercise therapy or other AHA
             therapy) and is willing to undergo a 10-week metformin wash-off period

          -  Have an estimated glomerular filtration rate (eGFR) of ≥30 to <60 mL/min/1.73m^2

          -  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)

          -  History of nephrotic range proteinuria with hypoalbuminemia and edema

          -  History of rapidly progressive glomerulonephritis, lupus nephritis, renal or systemic
             vasculitis, renal artery stenosis with renovascular hypertension, or ischemic
             nephropathy

          -  History of familial renal glucosuria

          -  History of renal dialysis or renal transplant or renal disease requiring treatment
             with any immunosuppressive agent

          -  A known hypersensitivity or intolerance to any (sodium-glucose co-transporter 2) SGLT2
             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

          -  Has been treated with rosiglitazone or other SGLT2 inhibitors 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 non-alcoholic 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 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