Clinical trial NCT03940742: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Insufficiency
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-05-07
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide
timeFrame: Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose
measure: PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide
timeFrame: Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose
Secondary outcomes:
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: New Orleans
country: United States
facility: New Orleans Center for Clinical Research
state: Louisiana
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
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.