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

Phase 1

Terminated

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Part A: U-500R Single Injection	U-500R	Bolus of U-500R administered via single subcutaneous (SC) injection.
Part A: U-500R CSII	U-500R	Bolus of U-500R administered via continuous subcutaneous insulin infusion (CSII).
Part B: U-500R BID	U-500R	U-500R administered twice-daily (BID) via SC injection under steady state conditions for 5 to 10 days
Part B: U-500R TID	U-500R	U-500R administered thrice-daily (TID) via SC injection under steady state conditions for 5 to 10 days

Primary Outcome Measures

Name	Time	Method
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: Area Under the Concentration Versus Time Curve from Zero to 24 Hours Postdose (AUC\[0-24\]) of U-500R.
Part B: 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	Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) 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 A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R.
Part B: 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	Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax) of U-500R.

Secondary Outcome Measures

Name	Time	Method
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 A: Pharmacodynamics (PD): Time to Rmax (tRmax) 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: Pharmacokinetics: Time to Maximum Concentration (Tmax) 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	Part B: Pharmacodynamics: Time to Rmax (tRmax) 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: 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 B: 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	Pharmacodynamics: Total Amount of Glucose Infused (Gtot) of U-500R.

Locations (1): Profil Institute for Clinical Research
🇺🇸
Chula Vista, California, United States