Hepatic InsufficiencyPhase 1NCT03940742

A Study of Tirzepatide in Participants With Impaired Liver Function

A Phase 1 study testing Tirzepatide in people with Hepatic Insufficiency, run by Eli Lilly and Company at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 85 yearsHealthy volunteers can take part
Conditions the study is for: Hepatic Insufficiency
What is being tested?: Tirzepatide
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 3 sitesUnited States
Study dates: 22 Jul 2019to 22 Sep 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Show all 10Show fewer

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

Who cannot join

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)

Show all 9Show fewer

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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

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

Other trials in United States

About this study

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

Conditions: Hepatic Insufficiency
Being tested: Tirzepatide
Medical subject headings: Hepatic Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TirzepatideDrug
Also called LY3298176
Administered SC

Study groups in NCT03940742
Study group	Role	What they receive
Normal Hepatic Function	Active comparator	Participants with normal hepatic function received single subcutaneous dose of 5 milligrams (mg) tirzepatide. Receives: Drug: Tirzepatide
Mild Hepatic Impairment	Experimental	Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. Receives: Drug: Tirzepatide
Moderate Hepatic Impairment	Experimental	Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. Receives: Drug: Tirzepatide
Severe Hepatic Impairment	Experimental	Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. Receives: Drug: Tirzepatide

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Jul 201922 Sep 2020

First posted7 May 2019
Study start22 Jul 2019
Primary completion22 Sep 2020
Study completion22 Sep 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatic InsufficiencyStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03940742
Sponsor's protocol ID: 17102
Other IDs: I8F-MC-GPGQ
Status last verified: 1 Jun 2022
First submitted: 6 May 2019
Last updated: 24 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 35674880

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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LiverPAL: A Trial of Inpatient Palliative Care for Patients With Advanced Liver Disease
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All Hepatic Insufficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Dose Pharmacokinetic Study of Tirzepatide in Subjects With Varying Degrees of Hepatic Impairment
ClinicalTrials.gov ID: NCT03940742
Acronym / sponsor ID: 17102
Conditions: Hepatic Insufficiency
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: 22 Jul 2019 (actual)
Primary completion: 22 Sep 2020 (actual)
Study completion: 22 Sep 2020 (actual)
First posted: 7 May 2019 (actual)
Results: Posted 24 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Normal Hepatic Function	Active comparator	Drug: TirzepatideParticipants with normal hepatic function received single subcutaneous dose of 5 milligrams (mg) tirzepatide.
Mild Hepatic Impairment	Experimental	Drug: TirzepatideParticipants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
Moderate Hepatic Impairment	Experimental	Drug: TirzepatideParticipants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
Severe Hepatic Impairment	Experimental	Drug: TirzepatideParticipants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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 males or females as determined by medical history, physical examination, and other screening procedures, with normal liver function
Males or females with chronic mild, moderate and severe liver impairment, assessed by Child-Pugh scoring

Key exclusion criteria (9 listed)

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
Have hemoglobin <8.5 grams per deciliter (g/dL)
Have kidney function that is significantly impaired at screening

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TirzepatideAlso: LY3298176Administered SC	Drug	Mild Hepatic Impairment, Moderate Hepatic Impairment, Normal Hepatic Function, Severe Hepatic Impairment

Primary outcome

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

Results and safety

Results posted to the registry on 24 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control (Normal Hepatic Function)	13	13
Mild Hepatic Impairment	6	6
Moderate Hepatic Impairment	6	6
Severe Hepatic Impairment	7	6

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram*hour per milliliter (ng*h/mL)

Measure	Control (Normal Hepatic Function) n = 13	Mild Hepatic Impairment n = 6	Moderate Hepatic Impairment n = 6	Severe Hepatic Impairment n = 6
Value	84300 (28)	102000 (16)	82000 (29)	77000 (33)

Control (Normal Hepatic Function) vs Mild Hepatic Impairment: Ratio of geometric least squares mean: 1.08 (90% CI 0.879 to 1.32)
Control (Normal Hepatic Function) vs Moderate Hepatic Impairment: Ratio of geometric least squares mean: 0.960 (90% CI 0.790 to 1.17)
Control (Normal Hepatic Function) vs Severe Hepatic Impairment: Ratio of geometric least squares mean: 0.852 (90% CI 0.699 to 1.04)

Population analysed: All participants who received at least one dose of study drug and had evaluable PK data.

Primary outcome: PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide

Time frame: Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Control (Normal Hepatic Function) n = 13	Mild Hepatic Impairment n = 6	Moderate Hepatic Impairment n = 6	Severe Hepatic Impairment n = 7
Value	510 (28)	509 (18)	516 (44)	521 (23)

Control (Normal Hepatic Function) vs Mild Hepatic Impairment: Ratio of geometric least squares mean: 0.916 (90% CI 0.726 to 1.16)
Control (Normal Hepatic Function) vs Moderate Hepatic Impairment: Ratio of geometric least squares mean: 1.00 (90% CI 0.802 to 1.25)
Control (Normal Hepatic Function) vs Severe Hepatic Impairment: Ratio of geometric least squares mean: 0.972 (90% CI 0.784 to 1.21)

Population analysed: All participants who received at least one dose of study drug and had evaluable PK data.

Adverse events

Time frame: Baseline to Study Completion (Up to 14 Months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control (Normal Hepatic Function)	0 of 13 (0%)	4 of 13 (30.8%)	0 of 13
Mild Hepatic Impairment	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Moderate Hepatic Impairment	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Severe Hepatic Impairment	1 of 7 (14.3%)	2 of 7 (28.6%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35674880Urva 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.
A Study of Tirzepatide in Participants With Impaired Liver FunctionLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Hepatic Insufficiency

Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
Active, not recruiting
LiverPAL: A Trial of Inpatient Palliative Care for Patients With Advanced Liver Disease
Liver Disease Chronic, End Stage Liver DIsease
RecruitingObservational study
Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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) study director

Eli Lilly and Company

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tirzepatide in people with Hepatic Insufficiency, run by Eli Lilly and Company at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03940742, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2023.