A Study of LY2605541 and Glargine and Exercise in Participants With Type 1 Diabetes

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Drug: LY2605541; Drug: Insulin Glargine

• Registration Number: NCT01784211
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The purpose of this study is to measure how much of the study drug or insulin glargine gets into the blood stream and how long it takes the body to get rid of it. The effect of exercise will also be evaluated.

This study has two parts. In Part A, each participant will receive a daily injection of LY2605541 or insulin glargine for about 15 days. Some participants may continue into Part B. In Part B, participants will receive a daily injection of LY2605541 or insulin glargine with or without exercise. Part B lasts about 6 days.

Participants will remain on their regular physician-prescribed mealtime insulin throughout the study.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-02
• Study First Submitted: 2013-02-01
• Study First Submitted QC: 2013-02-01
• Study First Posted: 2013-02-05
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Results First Submitted: 2018-03-16
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-13
• Last Update Submitted: 2019-03-13
• Results First Posted: 2019-03-15
• Last Update Posted: 2019-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

• Are males or females that have had a diagnosis of Type I Diabetes Mellitus (T1DM) for at least 12 months and are receiving multiple daily insulin injections. Total daily insulin dose <1.2 units per kilogram per day (U/kg/day); daily basal dose >0.2 U/kg/day
• Female participants: are women of child-bearing potential who test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control during the study
• Have a body mass index (BMI) of 18 to 30 kilograms per meter squared (kg/m^2), inclusive
• Have a fasting c-peptide <0.3 nanomoles per liter (nmol/L)
• Have a hemoglobin A1c (HbA1c) <9% at screening

Participants with T1DM are eligible for enrollment in Part B of the study only if they meet all of the following criteria:

• Have a maximal oxygen uptake (VO2 max) of ≥25 milliliters (mL) of oxygen per kilogram per minute (O2/kg/min) (for women) or ≥30 mL O2/kg/min (for men)
• Perform regular physical cardiorespiratory activity to achieve an average total energy expenditure of ≥500 metabolic equivalent of task (MET)-minutes per week during the last 3 months prior to screening

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Exclusion Criteria

• Have known allergies to LY2605541, insulin glargine, related compounds or any components of the formulation
• Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from T1DM), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
• Have had episodes of severe hypoglycemia in the past 6 months (severe hypoglycemia is defined as having neurological symptoms consistent with neuroglycopenia and having required assistance in treatment by a second party)
• Have a history of hypoglycemia unawareness
• Regular use or intended use of any over-the-counter or prescription medications or nutritional supplements that may affect blood glucose, the body's sensitivity to insulin, or that promote weight loss within 14 days prior to dosing
• Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females), or are unwilling to comply with study requirements regarding alcohol consumption
• Currently smokes >5 cigarettes per day, or are unwilling to comply with study requirements regarding smoking or use of tobacco products
• Have a hemoglobin level <8.0 millimoles per liter (mmol/L) (male) or <6.4 mmol/L (female) at screening
• Are currently participating in a weight loss program or plan to do so during the course of the study
• Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, and intra-ocular preparations) or have received such therapy within the 4 weeks before dosing
• Have fasting triglycerides >400 milligrams per deciliter (mg/dL) (4.52 mmol/L)
• Have previous history or family history of deep vein thrombosis

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LY2605541 (Part A)	LY2605541	0.5 units per kilogram (U/kg) LY2605541 subcutaneously (SC) once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14. Participants remained on their regular physician-prescribed mealtime insulin.
First LY2605541 + Exercise,Then LY2605541 Alone (Part B)	LY2605541	0.5 U/kg LY2605541 SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 17 (no exercise on Day 20).Participants remained on their regular physician-prescribed mealtime insulin.
First LY2605541 Alone, Then LY2605541 + Exercise (Part B)	LY2605541	0.5 U/kg LY2605541 SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 20 (no exercise on Day 17). Participants remained on their regular physician-prescribed mealtime insulin.
First Glargine + Exercise, Then Glargine Alone (Part B)	Insulin Glargine	0.5 U/kg insulin glargine SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 17 (no exercise on Day 20). Participants remained on their regular physician-prescribed mealtime insulin.
First Glargine Alone, Then Glargine + Exercise (Part B)	Insulin Glargine	0.5 U/kg insulin glargine SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 20 (no exercise on Day 17).
Glargine (Part A)	Insulin Glargine	0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14. Participants remained on their regular physician-prescribed mealtime insulin.

Primary Outcome Measures

Name	Time	Method
Part A: Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2605541 and Insulin Glargine: Intra-Participant Variability	Part A: Predose and 4, 8, 12, and 24 hours postdose on Days 8, 11, and 14	Venous blood samples for pharmacokinetic analysis were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.
Part A: Pharmacokinetics: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUCτ) of LY2605541 and Insulin Glargine: Intra-Participant Variability	Part A: Predose and 4, 8, 12, and 24 hours postdose on Days 8, 11, and 14	Venous blood samples for pharmacokinetic analysis were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.

Secondary Outcome Measures

Name	Time	Method
Part B: Pharmacokinetics: AUCτ of LY2605541 and Insulin Glargine: Exercise Versus Non-Exercise	Part B: Predose, 11 hours postdose, every 30 minutes from 16.5 to 20 hours postdose, and 24 hours postdose on Day 16 or 19	Venous blood samples for pharmacokinetic analysis were collected in Part B. Results were stratified by whether or not the participant was undergoing an exercise challenge (+ Exercise) at the time of sample collection.
Part B: Pharmacokinetics: Cmax of LY2605541 and Insulin Glargine: Exercise Versus Non-Exercise	Part B: Predose, 11 hours postdose, every 30 minutes from 16.5 to 20 hours postdose, and 24 hours postdose on Day 16 or 19	Venous blood samples for pharmacokinetic analysis were collected in Part B. Results were stratified by whether or not the participant was undergoing an exercise challenge (+ Exercise) at the time of sample collection.
Part A: Pharmacodynamics: Total Amount of Glucose Infused Over the Duration of the Clamp (Gtot): Intra-Participant Variability	Part A: Predose up to 24 hours postdose on Days 8, 11, and 14	Glucodynamic measurements were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.

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.; 🇩🇪 Neuss, Germany