Clinical trial NCT02588950: A Study of U-500 Insulin (LY041001) in Participants With Type 2 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-10-28
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R
timeFrame: Period 1 and 2: -0.5, 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24 hours (h) post dose
measure: Part B: Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to 24 Hours Postdose (AUC[0-24]) of U-500R
timeFrame: Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
measure: Part B: Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of U-500R
timeFrame: Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
measure: Part B: Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax) of U-500R
timeFrame: Period 3 day 1: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18h post dose
Secondary outcomes:
measure: 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
timeFrame: Period 1 and 2: -0.5, 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24h post dose
measure: Part A: Pharmacodynamics (PD): Time to Rmax (tRmax) of U-500R
timeFrame: Period 1 and 2: 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24h post dose
measure: Part B: Pharmacokinetics: Time to Maximum Concentration (Tmax) of U-500R
timeFrame: Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
measure: Part B: Pharmacodynamics: Total Amount of Glucose Infused (Gtot) of U-500R
timeFrame: Period 3: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
measure: Part B: Pharmacodynamics: Time to Rmax (tRmax) of U-500R
timeFrame: Period 3: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dose
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research
state: California
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: