A Study of Tirzepatide in Participants With Impaired Liver 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 liver function compared to healthy participants. The study will last about two months and will include five visits to the study center.

Official Title
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A Single Dose Pharmacokinetic Study of Tirzepatide in Subjects With Varying Degrees of Hepatic Impairment

Conditions
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Hepatic Insufficiency

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 of childbearing potential are excluded from the study. 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 liver function Participants with Impaired Liver Function: Males or females with chronic mild, moderate and severe liver impairment, assessed by Child-Pugh scoring Have type 2 diabetes mellitus (T2DM) controlled with diet or exercise alone or on stable doses of metformin for at least 8 weeks Have a hemoglobin A1c (HbA1c) ≥6.0% and ≤11.0% at screening Exclusion Criteria: All Participants: 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 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 Impaired Liver Function: Have hemoglobin <8.5 grams per deciliter (g/dL) Have kidney function that is significantly impaired at screening Have taken any glucose-lowering medications other than metformin, including insulin, in the past 3 months before screening Have brain function impaired significantly due to liver condition

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Normal Hepatic Function<br>Participants with normal hepatic function received single subcutaneous dose of 5 milligrams (mg) tirzepatide. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: Mild Hepatic Impairment<br>Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: Moderate Hepatic Impairment<br>Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: Severe Hepatic Impairment<br>Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. | 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 Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide | Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide. | Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose | 
| PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide. | Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose |