Hepatic Insufficiency
Conditions
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.
Interventions
DRUGTirzepatide
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose | PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control (Normal Hepatic Function) Participants with normal hepatic function received single subcutaneous dose of 5 mg tirzepatide. | 13 |
| Mild Hepatic Impairment Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. | 6 |
| Moderate Hepatic Impairment Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. | 6 |
| Severe Hepatic Impairment Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide. | 7 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Control (Normal Hepatic Function) | Total | Severe Hepatic Impairment | Moderate Hepatic Impairment | Mild Hepatic Impairment |
|---|---|---|---|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 11.3 | 57.4 years STANDARD_DEVIATION 10.8 | 60.4 years STANDARD_DEVIATION 6.6 | 51.3 years STANDARD_DEVIATION 15.4 | 63.2 years STANDARD_DEVIATION 4.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 28 Participants | 7 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 28 Participants | 7 Participants | 6 Participants | 4 Participants |
| Region of Enrollment United States | 13 Participants | 32 Participants | 7 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 2 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 24 Participants | 5 Participants | 5 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 6 | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 4 / 13 | 2 / 6 | 2 / 6 | 2 / 7 |
| serious Total, serious adverse events | 0 / 13 | 0 / 6 | 0 / 6 | 1 / 7 |
Outcome results
Primary
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.
Time frame: Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Control (Normal Hepatic Function) | Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide | 84300 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 28 |
| Mild Hepatic Impairment | Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide | 102000 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 16 |
| Moderate Hepatic Impairment | Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide | 82000 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 29 |
| Severe Hepatic Impairment | Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide | 77000 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 33 |
90% CI: [0.879, 1.32]
90% CI: [0.79, 1.17]
90% CI: [0.699, 1.04]
Primary
PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide
PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide.
Time frame: Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Control (Normal Hepatic Function) | PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 510 ng/mL | Geometric Coefficient of Variation 28 |
| Mild Hepatic Impairment | PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 509 ng/mL | Geometric Coefficient of Variation 18 |
| Moderate Hepatic Impairment | PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 516 ng/mL | Geometric Coefficient of Variation 44 |
| Severe Hepatic Impairment | PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 521 ng/mL | Geometric Coefficient of Variation 23 |
90% CI: [0.726, 1.16]
90% CI: [0.802, 1.25]
90% CI: [0.784, 1.21]