Back to resultsA Study to Compare and Measure the Effects of Insulin Peglispro (LY2605541) and Glargine on Meal Time Insulin Requirements
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Insulin Peglispro
Insulin Lispro
Insulin Glargine
Sponsored by
About this trial
This is an interventional basic science trial for Diabetes Mellitus, Type 1
Eligibility Criteria
Inclusion Criteria:
- Have a stable (within 0.5 percent (%) from last measure) glycated hemoglobin (HbA1c) <9.0%
- Have a stable (within 30%) basal insulin dose of 0.2 to 1.0 units per kilogram per day (U/kg/day) and a total daily insulin dose (basal + prandial/bolus) <1.5 units per kilogram (U/kg)
- Have C-peptide <0.3 nanomoles per liter (nmol/L)
- Are able and willing to eat the protocol specified standard breakfast and other meals as required
Exclusion Criteria:
- Have corrected QT interval (QTc) prolongation >500 milliseconds (ms) or have any other abnormality in the 12 lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
- Have an abnormal blood pressure as determined by the investigator
- Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from Type 1 Diabetes Mellitus [T1DM]), hematological, or neurological disorders
- Have fasting triglycerides (TGs) >400 milligrams per deciliter (mg/dL) (4.52 micromoles per liter [mmol/L])
- Have used systemic corticosteroids within 4 weeks prior to randomization
- Currently receive insulin pump or insulin degludec
- Have poorly controlled diabetes or are known to have poor awareness of hypoglycemia
- Have history of gastroparesis or gastrointestinal malabsorption
- Require treatment with any drug other than insulin to treat diabetes
- Have a previous history of proliferative retinopathy
Sites / Locations
- 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.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Insulin peglispro (LY2605541, with Insulin Lispro)
Insulin Glargine (with Insulin Lispro)
Arm Description
Insulin peglispro (LY2605541) once daily subcutaneous (SC) injection at bedtime. Insulin lispro given SC prandially or as bolus as required
Insulin glargine once daily SC injection at bedtime. Insulin lispro given SC prandially or as a bolus as required
Outcomes
Primary Outcome Measures
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
To quantitate the pharmacodynamic (PD) effect of a range of prandial insulin lispro doses after treatment with insulin peglispro (LY2605541) compared to insulin glargine during a meal tolerance test (MTT), with sequenced doses of insulin lispro ranging from 25% to 150% of each participant's normal dose. Data presented as hours times milligrams per deciliter (mg*h/dL)
Secondary Outcome Measures
Pharmacokinetics (PK): Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro
Abbreviation for hours times picomol per liter (pmol*h/L)
Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)
Abbreviation for micro mole per kilogram per minute (µmol/kg/min). Both arms received insulin lispro in addition to their respective study drug. During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.
Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Last Time (AUC [0 Tlast]) for Paracetamol
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount.
The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount.
Day 29 and cumulative insulin lispro doses of 25%, 50%, 75%, 100% and 150 % of normal insulin lispro dose included.Scores were averaged will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints and reported in millimeters.
Pharmacodynamics (PD): Area Under the Concentration Zero Through 5 Hours (AUC 0-5h) for Triglycerides
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp
During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin (Low) of which the effect is largely on the liver and a high dose of insulin (high) at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. AUC is taking during infusion for this outcome measure.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02152384
Brief Title
A Study to Compare and Measure the Effects of Insulin Peglispro (LY2605541) and Glargine on Meal Time Insulin Requirements
Official Title
The Effect of Treatment With Basal Insulin Peglispro or Insulin Glargine on the Dose Response Effect of Prandial Insulin Lispro in Patients With Type 1 Diabetes Mellitus.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will look into how a base dose of insulin peglispro and insulin glargine will affect the meal time dose and efficacy of insulin lispro in type 1 diabetics.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Insulin peglispro (LY2605541, with Insulin Lispro)
Arm Type
Experimental
Arm Description
Insulin peglispro (LY2605541) once daily subcutaneous (SC) injection at bedtime. Insulin lispro given SC prandially or as bolus as required
Arm Title
Insulin Glargine (with Insulin Lispro)
Arm Type
Active Comparator
Arm Description
Insulin glargine once daily SC injection at bedtime. Insulin lispro given SC prandially or as a bolus as required
Intervention Type
Drug
Intervention Name(s)
Insulin Peglispro
Other Intervention Name(s)
LY2605541
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Insulin Lispro
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Insulin Glargine
Intervention Description
Administered SC
Primary Outcome Measure Information:
Title
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
Description
To quantitate the pharmacodynamic (PD) effect of a range of prandial insulin lispro doses after treatment with insulin peglispro (LY2605541) compared to insulin glargine during a meal tolerance test (MTT), with sequenced doses of insulin lispro ranging from 25% to 150% of each participant's normal dose. Data presented as hours times milligrams per deciliter (mg*h/dL)
Time Frame
Day 30, 31, 32, 33, 34, pre-breakfast and10,20,30,40,50,60,90,120,150,180,210,240,270, 300 minutes (5 hours) post-breakfast
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro
Description
Abbreviation for hours times picomol per liter (pmol*h/L)
Time Frame
Day 29: Pre-breakfast, and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast
Title
Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)
Description
Abbreviation for micro mole per kilogram per minute (µmol/kg/min). Both arms received insulin lispro in addition to their respective study drug. During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.
Time Frame
Day 35, last 60 minutes of euglycemic 2-step hyperinsulinemic clamp
Title
Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Last Time (AUC [0 Tlast]) for Paracetamol
Time Frame
Day 29: Pre-breakfast, and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast
Title
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Description
VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount.
The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount.
Day 29 and cumulative insulin lispro doses of 25%, 50%, 75%, 100% and 150 % of normal insulin lispro dose included.Scores were averaged will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints and reported in millimeters.
Time Frame
Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast
Title
Pharmacodynamics (PD): Area Under the Concentration Zero Through 5 Hours (AUC 0-5h) for Triglycerides
Time Frame
Day 29, predose and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast
Title
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp
Description
During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin (Low) of which the effect is largely on the liver and a high dose of insulin (high) at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. AUC is taking during infusion for this outcome measure.
Time Frame
Day 35, insulin clearance during lispro infusion (dosing=infusion)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have a stable (within 0.5 percent (%) from last measure) glycated hemoglobin (HbA1c) <9.0%
Have a stable (within 30%) basal insulin dose of 0.2 to 1.0 units per kilogram per day (U/kg/day) and a total daily insulin dose (basal + prandial/bolus) <1.5 units per kilogram (U/kg)
Have C-peptide <0.3 nanomoles per liter (nmol/L)
Are able and willing to eat the protocol specified standard breakfast and other meals as required
Exclusion Criteria:
Have corrected QT interval (QTc) prolongation >500 milliseconds (ms) or have any other abnormality in the 12 lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
Have an abnormal blood pressure as determined by the investigator
Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from Type 1 Diabetes Mellitus [T1DM]), hematological, or neurological disorders
Have fasting triglycerides (TGs) >400 milligrams per deciliter (mg/dL) (4.52 micromoles per liter [mmol/L])
Have used systemic corticosteroids within 4 weeks prior to randomization
Currently receive insulin pump or insulin degludec
Have poorly controlled diabetes or are known to have poor awareness of hypoglycemia
Have history of gastroparesis or gastrointestinal malabsorption
Require treatment with any drug other than insulin to treat diabetes
Have a previous history of proliferative retinopathy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
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.
City
Neuss
ZIP/Postal Code
41460
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
A Study to Compare and Measure the Effects of Insulin Peglispro (LY2605541) and Glargine on Meal Time Insulin Requirements
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