A Study of U-500 Insulin (LY041001) in Participants With Type 2 Diabetes

Comparative Pharmacokinetics and Pharmacodynamics of Human Regular U-500 Insulin Administered Subcutaneously as a Bolus Via Syringe Versus Continuous Subcutaneous Insulin Infusion and Characterization of TID and BID Dosing at Steady State in High-Dose Insulin-Treated Subjects With Type 2 Diabetes Mellitus

The purpose of this two-part study is to measure how much of the study drug gets into the blood stream and how long it takes the body to get rid of it. In Part A, each participant will receive two treatments, a single dose and a single dose with continuous infusion of U-500R insulin, both administered just under the skin. Participants who complete Part A will continue into Part B where they will be assigned to 1 of 2 treatments with U-500R insulin, injected either twice or three times daily under the skin for 5-10 days. This study can last from 7-14 weeks including initial screening and follow up.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: U-500R

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Profil Institute for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males or females with type 2 diabetes mellitus (T2DM)
• Are current users of U-100, U-200 and/or U-300 insulin/analog as, basal, premixed and/or basal/bolus delivered with any injection device (pens and/or syringe/vial but excluding continuous subcutaneous infusion (CSII)/insulin pump use in the preceding 3 months), taking a total daily dose (TDD) of greater than or equal to (≥) 150 units (U) or at least one dose greater than (>) 100 U as part of a multiple daily injection (MDI) regimen and TDD less than or equal to (≤)3.0 units per kilogram (U/kg)
• Concomitant antihyperglycemic agent(s) (AHA) therapy may include: metformin (MET), dipeptidyl peptidase 4 inhibitors, pioglitazone (doses ≤30 milligrams per day (mg/day)), glucagon like peptide (GLP)-1 receptor agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, except in combination with GLP-1 receptor agonists
• Participant's antihyperglycemic agent (AHA) therapy must have been stable for ≥3 months (except for weekly GLP-1 receptor agonists which must have been stable for ≥4 months)
• Have hemoglobin A1c (HbA1c) 7.5-11.5 percent (%)

Exclusion Criteria:

• Have type 1 diabetes mellitus (T1DM), or other types of diabetes mellitus apart from T2DM
• Have known hypersensitivities or allergies to insulin, excipients contained in insulin products, or related compounds
• Have used U-500R within 3 months prior to screening
• Have used rosiglitazone, pramlintide, once weekly or twice daily exenatide, or other injectable or oral antihyperglycemic agent(s) not listed in the inclusion criterion; or are taking oral antidiabetic medications at doses exceeding the respective product labels
• Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia which may affect reliability of HbA1c measurements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B: U-500R TID; U-500R administered thrice-daily (TID) via SC injection under steady state conditions for 5 to 10 days	Drug: U-500R; Other Names: LY041001; Humulin; Humulin R U-500
Experimental: Part B: U-500R BID; U-500R administered twice-daily (BID) via SC injection under steady state conditions for 5 to 10 days	Drug: U-500R; Other Names: LY041001; Humulin; Humulin R U-500
Experimental: Part A: U-500R Single Injection; Bolus of U-500R administered via single subcutaneous (SC) injection.	Drug: U-500R; Other Names: LY041001; Humulin; Humulin R U-500
Experimental: Part A: U-500R CSII; Bolus of U-500R administered via continuous subcutaneous insulin infusion (CSII).	Drug: U-500R; Other Names: LY041001; Humulin; Humulin R U-500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R	Part A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R.	Period 1 and 2: -0.5, 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24 hours (h) post dose
Part B: Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to 24 Hours Postdose (AUC[0-24]) of U-500R	Part B: Pharmacokinetics: Area Under the Concentration Versus Time Curve from Zero to 24 Hours Postdose (AUC[0-24]) of U-500R.	Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
Part B: Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of U-500R	Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of U-500R.	Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
Part B: Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax) of U-500R	Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax) of U-500R.	Period 3 day 1: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18h post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Pharmacokinetics: Area Under The Concentration Versus Time Curve From Time Zero to Last Time Point With A Measurable Concentration (AUC[0-tlast]) of U-500R	Part A: Pharmacokinetics: Area Under The Concentration Versus Time Curve From Time Zero to Last Time Point With A Measurable Concentration (AUC[0-tlast]) of U-500R.	Period 1 and 2: -0.5, 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24h post dose
Part A: Pharmacodynamics (PD): Time to Rmax (tRmax) of U-500R	Part A: Pharmacodynamics (PD): Time to Rmax (tRmax) of U-500R.	Period 1 and 2: 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24h post dose
Part B: Pharmacokinetics: Time to Maximum Concentration (Tmax) of U-500R	Part B: Pharmacokinetics: Time to Maximum Concentration (Tmax) of U-500R.	Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
Part B: Pharmacodynamics: Total Amount of Glucose Infused (Gtot) of U-500R	Pharmacodynamics: Total Amount of Glucose Infused (Gtot) of U-500R.	Period 3: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
Part B: Pharmacodynamics: Time to Rmax (tRmax) of U-500R	Part B: Pharmacodynamics: Time to Rmax (tRmax) of U-500R.	Period 3: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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

Publications and helpful links

Helpful Links

• Click here for more information about this study: A Study of U-500 Insulin (Humulin LY041001) in Participants With Type 2 Diabetes

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2016
• Primary Completion (Actual): May 25, 2017
• Study Completion (Actual): May 25, 2017

Study Registration Dates

• First Submitted: October 27, 2015
• First Submitted That Met QC Criteria: October 27, 2015
• First Posted (Estimated): October 28, 2015

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin, Isophane
• Other Study ID Numbers: 16021; B5K-EW-IBHG (Other Identifier: Eli Lilly and Company)