A Study of How Insulin Peglispro (LY2605541) and Insulin Glargine Affect the Breakdown of Fat and Sugar in Type 1 Diabetics

Evaluation of the Effects of Insulin Peglispro (LY2605541) on Respiratory Quotient During Sleep and Response to Hyperinsulinemia Compared With That of Insulin Glargine in Patients With Type 1 Diabetes Mellitus

This is a two-period study of participants with type 1 diabetes mellitus (T1DM). In each period, participants will receive once daily injections of stable dose LY2605541 or insulin glargine for 28 to 35 days followed by procedures to look at how the body uses or stores fats and sugars. Participants will continue to use meal time insulin throughout the study. Healthy participants will also enroll in the study. They will not receive any study medication.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Biological: LY2605541; Biological: Insulin Glargine

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32804
      • Translational Research Institute for Metabolism and Diabetes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Type 1 Diabetics:

- T1DM for more than 1 year with Hemoglobin A1c (HbA1c) of less than 9.5%

All Participants:

• Otherwise fit and healthy
• Non smoker

Exclusion Criteria:

Type 1 Diabetics:

• Taking medication or supplements other than insulin to control diabetes
• Suffered a hypoglycemic event in the last 12 months that required hospitalization or have poor awareness of hypoglycemia

All Participants:

- Taking fibrates, thyroid replacement therapy, testosterone, beta blockers or systemic corticosteroids

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Peglispro/Insulin Glargine; Insulin peglispro (LY2605541) administered to participants with T1DM subcutaneously (SQ) once daily (QD) for 28 to 35 days in one of two treatment periods. Dose is based on participant's prestudy basal insulin dosing regimen. Insulin glargine administered to participants with T1DM SQ QD for 28 to 35 days in one of two treatment periods. Dose is based on participant's prestudy basal insulin dosing regimen. Participants continue to use mealtime insulin.	Biological: LY2605541; Administered SQ
Active Comparator: Insulin Glargine/Insulin Peglispro; Insulin glargine administered to participants with T1DM SQ QD for 28 to 35 days in one of two treatment periods. Dose is based on participant's prestudy basal insulin dosing regimen. Participants continue to use mealtime insulin. Insulin peglispro (LY2605541) administered to participants with T1DM subcutaneously (SQ) once daily (QD) for 28 to 35 days in one of two treatment periods. Dose is based on participant's prestudy basal insulin dosing regimen.	Biological: Insulin Glargine; Administered SQ
No Intervention: Control; Control Arm. Untreated healthy participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Respiratory Quotient (RQ) in Type 1 Diabetes Mellitus (T1DM)	Lipid or glucose metabolism was assessed by the measurement of respiratory quotient (RQ) during sleep using whole room calorimetry. RQ is a calculation of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry (WRC).	Day 30 post dose, overnight period (0000 to 0600 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid Oxidation in T1DM and Healthy Participants	Lipid oxidation is derived from RQ, basal metabolic rate and urinary nitrogen, a value of 0.7 indicates that lipids are being metabolized.	Day 30 post dose, overnight period (0000 to 0600 hours)
Basal Metabolic Rate (BMR) for T1DM	BMR is the metabolic rate determined at rest 12 to 14 hours after the last meal.	Day 30 post dose, overnight period (0000 to 0600 hours)
Sleep Respiratory Quotient (RQ) of Untreated Healthy Participants	The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry. The overnight period was averaged based on all 1-minutes interval measurements for the duration of the overnight period.	Day 5, overnight period (0000 to 0600 hours)
Total Number of Minutes of Lipid Oxidation (RQ Below 7.6) in T1DM and Healthy Participants	The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry.It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole data based on all 1-minutes interval measurements for the duration of the overnight period.	Day 5, every minute through 23 hour period
Change in RQ, Pre-breakfast to Post-breakfast Meal, in T1DM	The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry.	Day 30 0830 to 0854 hours, Day 30 1000 to 1054 hours

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: August 16, 2013
• First Submitted That Met QC Criteria: August 16, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Actual): March 1, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Glargine
• Other Study ID Numbers: 14872; I2R-MC-BIDO (Other Identifier: Eli Lilly and Company)