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

NCT03482024 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17021I8F-MC-GPGG
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 4

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.

Conditions

Renal Insufficiency; End Stage Renal Disease

Outcome Measures

Primary Outcomes (3)

• 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.

  Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose

• PK: Maximum Concentration of Tirzepatide

  Cmax is the maximum observed concentration of Tirzepatide.

  Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose

• 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.

  Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose

Study Arms (5)

Tirzepatide - Control

EXPERIMENTAL

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

Drug: Tirzepatide

Tirzepatide - Mild Renal Impairment

EXPERIMENTAL

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

Drug: Tirzepatide

Tirzepatide - Moderate Renal Impairment

EXPERIMENTAL

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

Drug: Tirzepatide

Tirzepatide - Severe Renal Impairment

EXPERIMENTAL

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

Drug: Tirzepatide

Tirzepatide - End Stage Renal Disease (ESRD)

EXPERIMENTAL

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

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Administered SC.

Also known as: LY3298176

Tirzepatide - Control; Tirzepatide - End Stage Renal Disease (ESRD); Tirzepatide - Mild Renal Impairment; Tirzepatide - Moderate Renal Impairment; Tirzepatide - Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (4)

Orange County Research Center

Tustin, California, 92780, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

High Point Clinical Trials Center

High Point, North Carolina, 27265, United States

Location

Related Publications (1)

• Urva S, Quinlan T, Landry J, Martin J, Loghin C. Effects of Renal Impairment on the Pharmacokinetics of the Dual GIP and GLP-1 Receptor Agonist Tirzepatide. Clin Pharmacokinet. 2021 Aug;60(8):1049-1059. doi: 10.1007/s40262-021-01012-2. Epub 2021 Mar 29.

  PMID: 33778934 DERIVED

MeSH Terms

Conditions

Renal Insufficiency; Kidney Failure, Chronic

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: March 29, 2018
• Study Start: March 30, 2018
• Primary Completion: August 19, 2019
• Study Completion: August 19, 2019
• Last Updated: March 23, 2023
• Results First Posted: March 23, 2023

Record last verified: 2022-06-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)