A Study of Tirzepatide (LY3298176) in Participants With Impaired Kidney Function
Condition: Renal Insufficiency; End Stage Renal Disease
MeSH terms: Kidney Failure, Chronic; Renal Insufficiency
Intervention: Tirzepatide
Intervention description: Administered SC.
Intervention MeSH terms: Tirzepatide
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to assess how fast tirzepatide gets into the blood stream and
      how long it takes the body to remove it in participants with impaired kidney function
      compared to healthy participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All Participants:

               -  Women not of childbearing potential may participate and include those who are
                  infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or
                  tubal ligation), congenital anomaly such as mullerian agenesis; or postmenopausal

               -  Are between the body mass index (BMI) of 19.0 and 40.0 kilograms per meter
                  squared (kg/m²), inclusive, at screening

          -  Healthy Participants:

             -- Healthy males or females as determined by medical history, physical examination,
             and other screening procedures, with normal renal function, assessed by estimated
             glomerular filtration rate (eGFR) ≥90 milliliters per minute (mL/min) at screening

          -  Participants with Renal Impairment or ESRD:

             -- Males or females with stable mild to severe renal impairment, assessed by eGFR or
             with ESRD (having received hemodialysis for at least 3 months)

          -  Participants with Type 2 Diabetes Mellitus (T2DM) and Renal Impairment or ESRD:

               -  Have T2DM controlled with diet or exercise alone or stable on metformin for at
                  least 8 weeks

               -  Taking stable doses of over-the-counter or prescription medications (eg,
                  antihypertensive agents, aspirin, lipid-lowering agents) for treatment of
                  concurrent medical conditions are permitted to participate providing they have
                  been stable on their treatment regimen for at least 4 weeks

               -  Have a hemoglobin A1c (HbA1c) ≥7.0% and ≤11.0% at screening

        Exclusion Criteria:

          -  All Participants:

               -  Women of childbearing potential

               -  Have known allergies to tirzepatide or related compounds

               -  Have a personal or family history of medullary thyroid carcinoma or have multiple
                  endocrine neoplasia syndrome type 2

               -  Have serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2×
                  the upper limit of normal (ULN) or total bilirubin (TBL) >1.5× ULN

               -  Have a history or presence of pancreatitis (history of chronic pancreatitis or
                  idiopathic acute pancreatitis), elevation in serum amylase or lipase or GI
                  disorder (eg, relevant esophageal reflux or gall bladder disease) or any GI
                  disease which impacts gastric emptying (eg, gastric bypass surgery, pyloric
                  stenosis, with the exception of appendectomy) or could be aggravated by
                  glucagon-like peptide-1 (GLP-1) analogs or dipeptidyl peptidase IV (DPP-IV)
                  inhibitors

          -  Participants with Renal Impairment or ESRD:

               -  Have hemoglobin <8.5 grams per deciliter (g/dL) or significant active
                  hematological disease from causes other than underlying renal disease.

               -  Have used any drug indicated for medical care of the participant's renal
                  impairment, which is not established in dose and administered for at least 7 days
                  before LY3298176 administration

          -  Participants with T2DM and Renal Impairment or ESRD:

               -  Have taken any glucose-lowering medications other than metformin, including
                  insulin, in the past 3 months before screening

               -  Have had more than 1 episode of severe hypoglycemia, as defined by the American
                  Diabetes Association criteria, within 6 months before entry into the study or has
                  a history of hypoglycemia unawareness or poor recognition of hypoglycemic
                  symptoms