End Stage Renal Disease, Renal 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 kidney function compared to healthy participants.
Interventions
DRUGTirzepatide
Administered SC.
Sponsors
Eli Lilly and Company
Study design
Allocation
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 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 renal function, assessed by estimated glomerular filtration rate (eGFR) ≥90 milliliters per minute (mL/min) at screening * Participants with Renal Impairment or ESRD: \-- Males or females with stable mild to severe renal impairment, assessed by eGFR or with ESRD (having received hemodialysis for at least 3 months) * Participants with Type 2 Diabetes Mellitus (T2DM) and Renal Impairment or ESRD: * Have T2DM controlled with diet or exercise alone or stable on metformin for at least 8 weeks * Taking stable doses of over-the-counter or prescription medications (eg, antihypertensive agents, aspirin, lipid-lowering agents) for treatment of concurrent medical conditions are permitted to participate providing they have been stable on their treatment regimen for at least 4 weeks * Have a hemoglobin A1c (HbA1c) ≥7.0% and ≤11.0% at screening
Exclusion criteria
* All Participants: * Women of childbearing potential * 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 serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2× the upper limit of normal (ULN) or total bilirubin (TBL) \>1.5× ULN * 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 Renal Impairment or ESRD: * Have hemoglobin \<8.5 grams per deciliter (g/dL) or significant active hematological disease from causes other than underlying renal disease. * Have used any drug indicated for medical care of the participant's renal impairment, which is not established in dose and administered for at least 7 days before LY3298176 administration * Participants with T2DM and Renal Impairment or ESRD: * Have taken any glucose-lowering medications other than metformin, including insulin, in the past 3 months before screening * Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before entry into the study or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]) | Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to tlast (AUC\[0-tlast\]) of Tirzepatide was evaluated. |
| PK: Maximum Concentration of Tirzepatide | Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose | Cmax is the maximum observed concentration of Tirzepatide. |
| PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf]) | Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose | Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-inf\]) of Tirzepatide was evaluated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tirzepatide - Control Participants received single dose of 5mg Tirzepatide by subcutaneous injection. | 14 |
| Tirzepatide - Mild Renal Impairment Participants received single dose of 5mg Tirzepatide by subcutaneous injection. | 8 |
| Tirzepatide - Moderate Renal Impairment Participants received single dose of 5mg Tirzepatide by subcutaneous injection. | 8 |
| Tirzepatide - Severe Renal Impairment Participants received single dose of 5mg Tirzepatide by subcutaneous injection. | 7 |
| Tirzepatide - End Stage Renal Disease (ESRD) Participants received single dose of 5mg Tirzepatide by subcutaneous injection. | 8 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Tirzepatide - Control | Total | Tirzepatide - End Stage Renal Disease (ESRD) | Tirzepatide - Severe Renal Impairment | Tirzepatide - Moderate Renal Impairment | Tirzepatide - Mild Renal Impairment |
|---|---|---|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 7.6 | 60.3 years STANDARD_DEVIATION 10.1 | 52.9 years STANDARD_DEVIATION 7.2 | 60.3 years STANDARD_DEVIATION 9.3 | 68.8 years STANDARD_DEVIATION 14.1 | 63.3 years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 14 Participants | 0 Participants | 4 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 31 Participants | 8 Participants | 3 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 21 Participants | 8 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 22 Participants | 0 Participants | 6 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 14 Participants | 45 Participants | 8 Participants | 7 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 5 Participants | 15 Participants | 2 Participants | 1 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 30 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 8 | 0 / 8 | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 1 / 14 | 4 / 8 | 3 / 8 | 3 / 7 | 3 / 8 |
| serious Total, serious adverse events | 0 / 14 | 0 / 8 | 0 / 8 | 0 / 7 | 0 / 8 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast])
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to tlast (AUC\[0-tlast\]) of Tirzepatide was evaluated.
Time frame: Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide - Control | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]) | 78400 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 24 |
| Tirzepatide - Mild Renal Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]) | 81900 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 36 |
| Tirzepatide - Moderate Renal Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]) | 98300 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 32 |
| Tirzepatide - Severe Renal Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]) | 81200 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 9 |
| Tirzepatide - End Stage Renal Disease (ESRD) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]) | 88500 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 14 |
Primary
PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf])
Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-inf\]) of Tirzepatide was evaluated.
Time frame: Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide - Control | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf]) | 80500 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 25 |
| Tirzepatide - Mild Renal Impairment | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf]) | 84200 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 37 |
| Tirzepatide - Moderate Renal Impairment | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf]) | 10400 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 32 |
| Tirzepatide - Severe Renal Impairment | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf]) | 83000 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 10 |
| Tirzepatide - End Stage Renal Disease (ESRD) | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf]) | 93400 Nanogram*hour per Millilitre (ng*h/mL) | Geometric Coefficient of Variation 12 |
Primary
PK: Maximum Concentration of Tirzepatide
Cmax is the maximum observed concentration of Tirzepatide.
Time frame: Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose
Population: All participants who received at least one dose of study drug and had evaluable PK data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide - Control | PK: Maximum Concentration of Tirzepatide | 339 Nanogram per Millilitre (ng/mL) | Geometric Coefficient of Variation 21 |
| Tirzepatide - Mild Renal Impairment | PK: Maximum Concentration of Tirzepatide | 353 Nanogram per Millilitre (ng/mL) | Geometric Coefficient of Variation 42 |
| Tirzepatide - Moderate Renal Impairment | PK: Maximum Concentration of Tirzepatide | 369 Nanogram per Millilitre (ng/mL) | Geometric Coefficient of Variation 36 |
| Tirzepatide - Severe Renal Impairment | PK: Maximum Concentration of Tirzepatide | 417 Nanogram per Millilitre (ng/mL) | Geometric Coefficient of Variation 11 |
| Tirzepatide - End Stage Renal Disease (ESRD) | PK: Maximum Concentration of Tirzepatide | 347 Nanogram per Millilitre (ng/mL) | Geometric Coefficient of Variation 30 |