A Study of LY2605541 Versus Insulin Glargine on Blood Sugar

Phase 1

Completed

Conditions: Healthy Volunteers
Diabetes Mellitus, Type 1

Interventions: Drug: LY2605541
Other: Insulin glargine

Registration Number: NCT01654380

Lead Sponsor: Eli Lilly and Company

Brief Summary: LY2605541 is an investigational drug being developed for the treatment of diabetes mellitus. This study is designed to understand how the body handles the investigational drug, what effect this investigational drug has on the body, and how much should be given. This study will also measure how much of the investigational drug gets into the blood stream and how long it takes the body to get rid of it. The study has 2 parts: Part A will be conducted in healthy participants. Part B will be conducted in participants with type 1 diabetes mellitus (T1DM). This study will take approximately 10-14 days spread over 6-20 weeks, not including screening. Screening will be performed within 30 days of the start of the study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 22

Inclusion Criteria

All Participants

Are healthy males or participants with T1DM
Have a screening body mass index (BMI) of 20.0-29.9 kilograms per square meter (kg/m^2)

Healthy Participants ONLY

Are overtly healthy, as determined by medical history and physical examination
Have a fasting blood glucose <108 milligrams/deciliter (mg/dL) (6.0 millimoles/liter [mmol/L]) at screening

Participants with T1DM ONLY

Have a diagnosis of T1DM for at least 1 year based on medical history
Have a screening c-peptide <0.5 nanograms/milliliter (ng/mL)
Have a hemoglobin A1c (HbA1c) of 6.0 to 9.0% at screening
Have had no episodes of severe hypoglycemia in the past 6 months

Exclusion Criteria

All Participants

Have a hemoglobin level <12.0 grams/deciliter (g/dL)
Are currently a smoker, used tobacco products on a regular basis in the 6 months prior to screening, or are intending to smoke during the study

Healthy Participants ONLY

• Regular use or intended use of over-the counter or prescription medication within 7 and 14 days, respectively, prior to dosing (apart from vitamin/mineral supplements or occasional use of acetaminophen or ibuprofen).

Participants with T1DM ONLY

Regular use or intended use of any over-the-counter or prescription medications or nutritional supplements that affect blood glucose or the body's sensitivity to insulin or that promote weight loss within 14 days prior to dosing
Are receiving chronic (lasting longer than 14 consecutive days) systemic or inhaled glucocorticoid therapy (excluding topical, intra-articular, and intraocular preparations) or have received such therapy within the 4 weeks before dosing
Require a total daily insulin dose exceeding 100 units (U)
Have fasting triglycerides >400 mg/dL

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part A, Cohort A; LY2605541	LY2605541	Healthy participants received 5.1 milliunits/minute (mU/min) in Period 1, 10.2 mU/min in Period 2, and 15.3 mU/min in Period 3, administered intravenously (IV) over 8 hours. All periods were separated by a minimum 6-day washout period
Part A, Cohort A; Insulin Glargine	Insulin glargine	Healthy participants received insulin glargine (30 milliunits/meter squared/minute \[mU/m\^2/min\]) administered IV over 8 hours in Period 4. All periods were separated by a minimum 6-day washout period
Part A, Cohort B; Insulin Glargine	Insulin glargine	Healthy participants received insulin glargine (60 mU/m\^2/min) administered IV over 8 hours in Period 4. All periods were separated by a minimum 6-day washout period.
Part B; LY2605541	LY2605541	Participants with T1DM received 15.3 mU/min in 1 of 4 study periods, administered IV up to 8 hours and received 74.1 mU/min in 1 of 4 Periods, administered IV up to 10 hours. Each dose was separated by a minimum 6-day washout period.
Part B; Insulin Glargine	Insulin glargine	Participants with T1DM received 1 insulin glargine dose per study period (10 and 20 mU/m\^2/min) administered IV over 8 hours in 2 of 4 study periods. Each dose was separated by a minimum 6-day washout period.
Part A, Cohort B; LY2605541	LY2605541	Healthy participants received 15.3 mU/min in Period 1, 37.0 mU/min in Period 2, and 74.1 mU/min in Period 3, administered IV over 8 hours. All periods were separated by a minimum 6-day washout period.

Primary Outcome Measures

Name	Time	Method
Part B: Glucodynamics: Endogenous Glucose Output	Baseline, up to 10 hours (duration of the euglycemic glucose clamp)	The percent suppression from baseline in endogenous glucose production (EGP) is presented. Percent EGP change from baseline was calculated by (1-\[last 2 hours of EGP/basal EGP\])\*100. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
Part B: Glycodynamics: Maximum Rate of Glucose Disposal	Baseline, up to 10 hours (duration of the euglycemic glucose clamp)	The maximum rate of glucose disposal (Rdmax) is presented. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
Part B: Glycodynamics: Glucose Disposal	Baseline, up to 10 hours (duration of the euglycemic glucose clamp)	The fold change from baseline in glucose disappearance rate (GDR) is presented. The fold GDR increase from baseline was calculated by last 2 hours of GDR/basal GDR. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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San Diego, California, United States