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A Study of Tirzepatide in Participants With Impaired Liver Function

Primary Purpose

Hepatic Insufficiency

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tirzepatide

About this trial

This is an interventional basic science trial for Hepatic Insufficiency

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Orange County Research Center
Orlando Clinical Research Center
New Orleans Center for Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Normal Hepatic Function

Mild Hepatic Impairment

Moderate Hepatic Impairment

Severe Hepatic Impairment

Arm Description

Participants with normal hepatic function received single subcutaneous dose of 5 milligrams (mg) tirzepatide.

Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.

Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.

Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.

Outcomes

Primary Outcome Measures

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.

PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide

PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide.

Secondary Outcome Measures

Full Information

NCT ID

NCT03940742

First Posted

May 6, 2019

Last Updated

June 9, 2022

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT03940742

Brief Title

A Study of Tirzepatide in Participants With Impaired Liver Function

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 1, 2022

Overall Recruitment Status

Completed

Study Start Date

July 22, 2019 (Actual)

Primary Completion Date

September 22, 2020 (Actual)

Study Completion Date

September 22, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief 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 liver function compared to healthy participants. The study will last about two months and will include five visits to the study center.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Insufficiency

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal Hepatic Function

Arm Type

Active Comparator

Arm Description

Participants with normal hepatic function received single subcutaneous dose of 5 milligrams (mg) tirzepatide.

Arm Title

Mild Hepatic Impairment

Arm Type

Experimental

Arm Description

Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.

Arm Title

Moderate Hepatic Impairment

Arm Type

Experimental

Arm Description

Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.

Arm Title

Severe Hepatic Impairment

Arm Type

Experimental

Arm Description

Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.

Intervention Type

Drug

Intervention Name(s)

Tirzepatide

Other Intervention Name(s)

LY3298176

Intervention Description

Administered SC

Primary Outcome Measure Information:

Title

Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide

Description

Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide.

Time Frame

Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose

Title

PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide

Description

PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide.

Time Frame

Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

Orange County Research Center

City

Tustin

State/Province

California

ZIP/Postal Code

92780

Country

United States

Facility Name

Orlando Clinical Research Center

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

Facility Name

New Orleans Center for Clinical Research

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35674880

Citation

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.

Results Reference

derived

Links:

URL

https://trials.lillytrialguide.com/en-US/trial/3Q0iEn37gojINvezSaoRkX

Description

A Study of Tirzepatide in Participants With Impaired Liver Function

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A Study of Tirzepatide in Participants With Impaired Liver Function

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