Phase 1 · Tirzepatide

NCT03482024 trial results

Pharmacokinetics of Tirzepatide Following Administration to Subjects With Impaired Renal Function

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]) (Nanogram*hour per Millilitre (ng*h/mL)), Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose. Tirzepatide - Control: 78400; Tirzepatide - Mild Renal Impairment: 81900; Tirzepatide - Moderate Renal Impairment: 98300; Tirzepatide - Severe Renal Impairment: 81200; Tirzepatide - End Stage Renal Disease (ESRD): 88500.

Participants
45
Status
completed
Completed
2019-08-19
Sponsor
Eli Lilly and Company

As posted on ClinicalTrials.gov (NCT03482024), updated at source Mar 23, 2023. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What NCT03482024 measured first

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast])Nanogram*hour per Millilitre (ng*h/mL) · Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose · geometric mean
Tirzepatide - Controln=13Tirzepatide - Mild Renal Impairmentn=8Tirzepatide - Moderate Renal Impairmentn=8Tirzepatide - Severe Renal Impairmentn=6Tirzepatide - End Stage Renal Disease (ESRD)n=8
78400(24)81900(36)98300(32)81200(9)88500(14)
PK: Maximum Concentration of TirzepatideNanogram per Millilitre (ng/mL) · Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose · geometric mean
Tirzepatide - Controln=13Tirzepatide - Mild Renal Impairmentn=8Tirzepatide - Moderate Renal Impairmentn=8Tirzepatide - Severe Renal Impairmentn=6Tirzepatide - End Stage Renal Disease (ESRD)n=8
339(21)353(42)369(36)417(11)347(30)
PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf])Nanogram*hour per Millilitre (ng*h/mL) · Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose · geometric mean
Tirzepatide - Controln=13Tirzepatide - Mild Renal Impairmentn=8Tirzepatide - Moderate Renal Impairmentn=8Tirzepatide - Severe Renal Impairmentn=6Tirzepatide - End Stage Renal Disease (ESRD)n=8
80500(25)84200(37)10400(32)83000(10)93400(12)
Side effects by arm

Side effects in NCT03482024

Percent of participants affected, Up to 28days. The most common events the registry lists.

EventTirzepatide - ControlTirzepatide - Mild Renal ImpairmentTirzepatide - Moderate Renal ImpairmentTirzepatide - Severe Renal ImpairmentTirzepatide - End Stage Renal Disease (ESRD)
Any serious event0%0%0%0%0%
Constipation0%25%0%0%0%
Vomiting0%0%0%14.3%25%
Anaemia0%0%0%14.3%0%
Diarrhoea0%12.5%12.5%14.3%0%
Headache7.1%0%0%14.3%0%
Orthostatic hypotension0%0%0%14.3%0%
Abdominal distension0%0%12.5%0%0%
Nausea0%12.5%0%0%12.5%
Contusion0%0%12.5%0%0%
Back pain0%12.5%12.5%0%0%
The trial

How NCT03482024 was run

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.

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

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...

Published papers

Papers from NCT03482024

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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