Effect of Renal Impairment on the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Ertugliflozin in Participants With Type 2 Diabetes Mellitus (MK-8835-009)
Condition: Renal Impairment; Type 2 Diabetes Mellitus
MeSH terms: Renal Insufficiency; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ertugliflozin
Intervention description: Single oral administration of 3 X 5 mg tablets.
Intervention MeSH terms: Ertugliflozin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a study to evaluate the effect of renal impairment on the pharmacokinetics,
      pharmacodynamics, safety and tolerability of ertugliflozin in participants with type 2
      diabetes mellitus (T2DM) and in healthy participants with normal renal function.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body Mass Index (BMI) of approximately 18 to 40 kg/m^2

          -  Stable renal function

          -  Male or female not of reproductive potential

          -  Female of reproductive potential must agree or have their partner agree to use 2
             acceptable methods of contraception

          -  Healthy subjects determined to be healthy by investigator screening

          -  T2DM participants have a diagnosis of T2DM as per American Diabetes Association
             guidelines

          -  T2DM participants to be on a stable anti-hyperglycemic regimen with no new drug or
             drug dosage within 8 weeks of study participation. Variations in daily dose of insulin
             up to 10% are permitted.

        Exclusion Criteria:

          -  A positive urine drug screen for drugs of abuse or recreational drugs

          -  Pregnant or nursing females

          -  History of abuse of alcohol or illicit drugs

          -  Significant renal or urinary disease within 6 months of study participation

          -  History of malignancy within the past 5 years basal cell carcinoma of the skin or
             cervical cancer in situ

          -  History of human immunodeficiency virus (HIV)

          -  History of blood dyscrasias or any disorders causing hemolysis or unstable red blood
             cells

          -  Any acute disease state (eg, , vomiting, fever, diarrhea) within 7 days before study
             participation

          -  Treatment with an investigational drug within 30 days of study participation

          -  Use of herbal supplements within 28 days prior to study participation

          -  Any clinically significant malabsorption condition

          -  Blood donation (excluding plasma donations) of approximately 1 pint within 56 days
             prior to study participation

          -  History of sensitivity to ertugliflozin or other Sodium-Glucose co-Transporter 2
             (SGLT2) inhibitors

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia

          -  Unwilling or unable to comply with the study Lifestyle Guidelines

          -  Evidence or history of clinically significant hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
             allergic disease including clinically relevant and significant drug allergies

          -  Use of prescription drugs (hormonal methods of birth control are allowed), vitamins
             and dietary supplements within 7 days of study participation

          -  For T2DM participants, history of type 1 diabetes mellitus or a history of
             ketoacidosis

          -  For T2DM participants, clinically significant electrocardiogram abnormality

          -  For T2DM participants, history of myocardial infarction, unstable angina, coronary
             revascularization, stroke or transient ischemic attack within 3 months of study
             participation

          -  For T2DM participants, heart failure defined as New York Heart Association Functional
             Class III-IV

          -  For T2DM participants, renal allograft recipients

          -  For T2DM participants, requiring dialysis

          -  For T2DM participants, strict fluid restriction

          -  For T2DM participants, urinary incontinence

          -  For T2DM participants, acute renal disease

          -  For T2DM participants, significant hepatic, cardiac, or pulmonary disease or
             clinically nephrotic

          -  For T2DM participants, prescription and over-the-counter medication that is not taken
             according to a stable regimen for 7 days before study participation

          -  For T2DM participants, on metformin should not be enrolled if their baseline renal
             function is outside the approved product labeling

          -  For T2DM participants receiving any of the following medications within 7 days of
             study participation: 1. Other SGLT2 inhibitors (eg, dapagliflozin, canagliflozin,
             empagliflozin); 2. Other injectable anti-hyperglycemic agents including pramlintide or
             Glucagon-like peptide-1 (GLP-1) analogues; 3. Any immunosuppressive drugs, including
             cyclosporine, tacrolimus, sirolimus; 4. Oral corticosteroids (note that inhaled, nasal
             and topical corticosteroids are permitted); 5. Any potent drug-metabolizing
             enzyme-inducing drug, including rifampin, phenytoin, and carbamazepine; 6. Probenecid,
             valproic acid, gemfibrozil.