A Study of Tirzepatide (LY3298176) in Participants With Impaired Kidney Function

Study Overview
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Brief Summary
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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.

Official Title
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Pharmacokinetics of Tirzepatide Following Administration to Subjects With Impaired Renal Function

Conditions
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Renal Insufficiency, End Stage Renal Disease

Intervention / Treatment
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* Drug: Tirzepatide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide - Control<br>Group 1 - Tirzepatide 5 milligrams (mg) administered subcutaneously (SC) to healthy participants with normal renal function. | Drug: Tirzepatide<br>* Administered SC.<br>* Other names: LY3298176;|
| Experimental: Tirzepatide - Mild Renal Impairment<br>Group 2 - Tirzepatide 5mg administered SC to participants with mild renal impairment. | Drug: Tirzepatide<br>* Administered SC.<br>* Other names: LY3298176;|
| Experimental: Tirzepatide - Moderate Renal Impairment<br>Group 3 - Tirzepatide 5mg administered SC to participants with moderate renal impairment. | Drug: Tirzepatide<br>* Administered SC.<br>* Other names: LY3298176;|
| Experimental: Tirzepatide - Severe Renal Impairment<br>Group 4 - Tirzepatide 5mg administered SC to participants with severe renal impairment. | Drug: Tirzepatide<br>* Administered SC.<br>* Other names: LY3298176;|
| Experimental: Tirzepatide - End Stage Renal Disease (ESRD)<br>Group 5 - Tirzepatide 5mg administered SC to participants with ESRD. | Drug: Tirzepatide<br>* Administered SC.<br>* Other names: LY3298176;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to tlast (AUC[0-tlast]) of Tirzepatide was evaluated. | Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose | 
| PK: Maximum Concentration of Tirzepatide | Cmax is the maximum observed concentration of Tirzepatide. | Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose | 
| PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf]) | Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC[0-inf]) of Tirzepatide was evaluated. | Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose |