A Study of Tirzepatide in Participants With Impaired Liver Function

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency
• Intervention / Treatment: Drug: Tirzepatide

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • New Orleans Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Normal Hepatic Function; Participants with normal hepatic function received single subcutaneous dose of 5 milligrams (mg) tirzepatide.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: Mild Hepatic Impairment; Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: Moderate Hepatic Impairment; Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: Severe Hepatic Impairment; Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Urva S, Quinlan T, Landry J, Ma X, Martin JA, Benson CT. Effects of Hepatic Impairment on the Pharmacokinetics of the Dual GIP and GLP-1 Receptor Agonist Tirzepatide. Clin Pharmacokinet. 2022 Jul;61(7):1057-1067. doi: 10.1007/s40262-022-01140-3. Epub 2022 Jun 8.

Helpful Links

• A Study of Tirzepatide in Participants With Impaired Liver Function

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Actual): September 22, 2020
• Study Completion (Actual): September 22, 2020

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 7, 2019

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 17102; I8F-MC-GPGQ (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes