NCT03940742

A Study of Tirzepatide in Participants With Impaired Liver Function

Completed Phase 1 Results posted Last updated 24 March 2023

What this trial tests

Phase 1 trial testing Tirzepatide in Hepatic Insufficiency in 32 participants. Completed in 22 September 2020.

Timeline

22 July 2019

Primary endpoint
22 September 2020

22 September 2020

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	32
Start date	22 July 2019
Primary completion	22 September 2020
Estimated completion	22 September 2020
Sites	3 locations across United States

Drugs / interventions tested

• Tirzepatide (TIRZEPATIDE) — full drug profile →

Conditions studied

• Hepatic Insufficiency — all drugs for Hepatic Insufficiency →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

Adults 18 to 85, any sex, with Hepatic Insufficiency. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide Primary · Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose

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

Group	Value	95% CI
Control (Normal Hepatic Function)	84300	± 28
Mild Hepatic Impairment	102000	± 16
Moderate Hepatic Impairment	82000	± 29
Severe Hepatic Impairment	77000	± 33

PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide Primary · Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose

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

Group	Value	95% CI
Control (Normal Hepatic Function)	510	± 28
Mild Hepatic Impairment	509	± 18
Moderate Hepatic Impairment	516	± 44
Severe Hepatic Impairment	521	± 23

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to Study Completion (Up to 14 Months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Control (Normal Hepatic Function)

Serious: 0/13 (0%)

Deaths: 0/13

Mild Hepatic Impairment

Serious: 0/6 (0%)

Deaths: 0/6

Moderate Hepatic Impairment

Serious: 0/6 (0%)

Deaths: 0/6

Severe Hepatic Impairment

Serious: 1/7 (14%)

Deaths: 0/7

Serious adverse events (1 terms)

Reaction	System	Control (Normal Hepatic Fu…	Mild Hepatic Impairment	Moderate Hepatic Impairment	Severe Hepatic Impairment
Hepatic encephalopathy	Nervous system disorders	—	—	—	—

Other adverse events (14 terms — click to expand)

Reaction	System	Control (Normal Hepatic Fu…	Mild Hepatic Impairment	Moderate Hepatic Impairment	Severe Hepatic Impairment
Nausea	Gastrointestinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—
Influenza like illness	General disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—

Most-reported serious reactions: Hepatic encephalopathy.

Data from ClinicalTrials.gov NCT03940742 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effects of Hepatic Impairment on the Pharmacokinetics of the Dual GIP and GLP-1 Receptor Agonist Tirzepatide.
   Urva S, Quinlan T, Landry J, Ma X, et al · · 2022 · cited 25× · PMID 35674880 · DOI 10.1007/s40262-022-01140-3
2. 57^th EASD Annual Meeting of the European Association for the Study of Diabetes.
   · 2021 · cited 11× · PMID 34468792 · DOI 10.1007/s00125-021-05519-y