Clinical trial NCT03482024: A Study of Tirzepatide (LY3298176) in Participants With Impaired Kidney Function
Official title: Pharmacokinetics of Tirzepatide Following Administration to Subjects With Impaired Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Insufficiency
End Stage Renal Disease
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2018-03-29
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast])
timeFrame: Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose
measure: PK: Maximum Concentration of Tirzepatide
timeFrame: Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose
measure: PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Infinity (AUC[0-inf])
timeFrame: Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose
Secondary outcomes:
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: High Point
country: United States
facility: High Point Clinical Trials Center
state: North Carolina
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.