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

Phase 1

Completed

• Conditions: End Stage Renal Disease; Renal Insufficiency
• Interventions: Drug: Tirzepatide

• Registration Number: NCT03482024
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-03-23
• Study First Submitted QC: 2018-03-23
• Study First Posted: 2018-03-29
• Study Start: 2018-03-30
• Primary Completion: 2019-08-19
• Study Completion: 2019-08-19
• Status Verified: 2022-06-01
• Results First Submitted: 2022-06-09
• Results First Submitted QC: 2022-06-09
• Last Update Submitted: 2022-06-09
• Results First Posted: 2023-03-23
• Last Update Posted: 2023-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tirzepatide - Control	Tirzepatide	Group 1 - Tirzepatide 5 milligrams (mg) administered subcutaneously (SC) to healthy participants with normal renal function.
Tirzepatide - Mild Renal Impairment	Tirzepatide	Group 2 - Tirzepatide 5mg administered SC to participants with mild renal impairment.
Tirzepatide - End Stage Renal Disease (ESRD)	Tirzepatide	Group 5 - Tirzepatide 5mg administered SC to participants with ESRD.
Tirzepatide - Moderate Renal Impairment	Tirzepatide	Group 3 - Tirzepatide 5mg administered SC to participants with moderate renal impairment.
Tirzepatide - Severe Renal Impairment	Tirzepatide	Group 4 - Tirzepatide 5mg administered SC to participants with severe renal impairment.

Primary Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (4)

Orange County Research Center; 🇺🇸 Tustin, California, United States

High Point Clinical Trials Center; 🇺🇸 High Point, North Carolina, United States

Clinical Pharmacology of Miami; 🇺🇸 Miami, Florida, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States