Intervention: Ertugliflozin
Trial phase: Phase 1
ATC code: A10BD23 | A10BD24 | A10BK04
SMILES: CCOc1ccc(Cc2cc([C@]34OC[C@](CO)(O3)[C@@H](O)[C@H](O)[C@H]4O)ccc2Cl)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 6
Group description: Ertugliflozin (15 mg), oral, administered in participants with T2DM and with severe renal impairment
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.