A Study of Tirzepatide (LY3298176) in Participants With Impaired Kidney Function

Lilly

Status and phase: Completed; Phase 1

Conditions: End Stage Renal Disease; Renal Insufficiency

Treatments: Drug: Tirzepatide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03482024

17021

I8F-MC-GPGG (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 45 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 5 patient groups

Tirzepatide - Control

Experimental group

Description:

Group 1 - Tirzepatide 5 milligrams (mg) administered subcutaneously (SC) to healthy participants with normal renal function.

Treatment:

Drug: Tirzepatide

Tirzepatide - Mild Renal Impairment

Experimental group

Description:

Group 2 - Tirzepatide 5mg administered SC to participants with mild renal impairment.

Treatment:

Drug: Tirzepatide

Tirzepatide - Moderate Renal Impairment

Experimental group

Description:

Group 3 - Tirzepatide 5mg administered SC to participants with moderate renal impairment.

Treatment:

Drug: Tirzepatide

Tirzepatide - Severe Renal Impairment

Experimental group

Description:

Group 4 - Tirzepatide 5mg administered SC to participants with severe renal impairment.

Treatment:

Drug: Tirzepatide

Tirzepatide - End Stage Renal Disease (ESRD)

Experimental group

Description:

Group 5 - Tirzepatide 5mg administered SC to participants with ESRD.

Treatment:

Drug: Tirzepatide