Trial Outcomes & Findings for A Study to Compare and Measure the Effects of Insulin Peglispro (LY2605541) and Glargine on Meal Time Insulin Requirements (NCT NCT02152384)
NCT ID: NCT02152384
Last Updated: 2019-03-01
Results Overview
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)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
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
Results posted on
2019-03-01
Participant Flow
Participant milestones
| Measure |
Treatment Sequence A/B
Treatment A: Insulin peglispro (LY2605541) once daily subcutaneous (SC). Insulin lispro given SC prandially or as bolus as required
Treatment B: Insulin glargine once daily subcutaneous (SC). Insulin lispro given SC prandially or as bolus as required
|
Treatment Sequence B/A
Treatment B: Insulin glargine once daily subcutaneous (SC). Insulin lispro given SC prandially or as bolus as required
Treatment A: Insulin peglispro (LY2605541) once daily subcutaneous (SC). Insulin lispro given SC prandially or as bolus as required
|
|---|---|---|
|
Run In (1-5 Week Transition)
STARTED
|
14
|
14
|
|
Run In (1-5 Week Transition)
COMPLETED
|
14
|
14
|
|
Run In (1-5 Week Transition)
NOT COMPLETED
|
0
|
0
|
|
Period 1
STARTED
|
14
|
14
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
14
|
14
|
|
Period 1
COMPLETED
|
13
|
12
|
|
Period 1
NOT COMPLETED
|
1
|
2
|
|
Period 2
STARTED
|
13
|
12
|
|
Period 2
COMPLETED
|
13
|
12
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence A/B
Treatment A: Insulin peglispro (LY2605541) once daily subcutaneous (SC). Insulin lispro given SC prandially or as bolus as required
Treatment B: Insulin glargine once daily subcutaneous (SC). Insulin lispro given SC prandially or as bolus as required
|
Treatment Sequence B/A
Treatment B: Insulin glargine once daily subcutaneous (SC). Insulin lispro given SC prandially or as bolus as required
Treatment A: Insulin peglispro (LY2605541) once daily subcutaneous (SC). Insulin lispro given SC prandially or as bolus as required
|
|---|---|---|
|
Period 1
Withdrawal by Subject
|
0
|
1
|
|
Period 1
Adverse Event
|
1
|
1
|
Baseline Characteristics
A Study to Compare and Measure the Effects of Insulin Peglispro (LY2605541) and Glargine on Meal Time Insulin Requirements
Baseline characteristics by cohort
| Measure |
All Participants
n=28 Participants
All randomized participants who received at least 1 dose of study drug.
|
|---|---|
|
Age, Continuous
|
44.2 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
28 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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-breakfastPopulation: All participants who received at least 1 dose of study drug and had evaluable PD data.
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)
Outcome measures
| Measure |
Insulin Peglispro (LY2605541)
n=27 Participants
Insulin peglispro (LY2605541) administered SC daily
|
Insulin Glargine
n=26 Participants
Insulin glargine administered SC daily
|
|---|---|---|
|
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
25% Normal Dose
|
677.84 mg*h/dL
Standard Deviation 146.48
|
716.52 mg*h/dL
Standard Deviation 179.89
|
|
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
50% Normal Dose
|
572.96 mg*h/dL
Standard Deviation 149.76
|
506.22 mg*h/dL
Standard Deviation 188.54
|
|
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
75% Normal Dose
|
393.28 mg*h/dL
Standard Deviation 175.68
|
369.08 mg*h/dL
Standard Deviation 169.08
|
|
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
100% Normal Dose
|
270.46 mg*h/dL
Standard Deviation 201.73
|
307.81 mg*h/dL
Standard Deviation 204.27
|
|
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
150% Normal Dose
|
174.38 mg*h/dL
Standard Deviation 182.00
|
123.97 mg*h/dL
Standard Deviation 118.82
|
SECONDARY outcome
Timeframe: Day 29: Pre-breakfast, and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfastPopulation: All participants who received at least 1 dose of study drug and had evaluable PK data.
Abbreviation for hours times picomol per liter (pmol\*h/L)
Outcome measures
| Measure |
Insulin Peglispro (LY2605541)
n=23 Participants
Insulin peglispro (LY2605541) administered SC daily
|
Insulin Glargine
n=21 Participants
Insulin glargine administered SC daily
|
|---|---|---|
|
Pharmacokinetics (PK): Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro
|
850 pmol*h/L
Geometric Coefficient of Variation 47
|
852 pmol*h/L
Geometric Coefficient of Variation 44
|
SECONDARY outcome
Timeframe: Day 35, last 60 minutes of euglycemic 2-step hyperinsulinemic clampPopulation: All participants who received at least 1 dose of study drug and had evaluable PD data.
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.
Outcome measures
| Measure |
Insulin Peglispro (LY2605541)
n=12 Participants
Insulin peglispro (LY2605541) administered SC daily
|
Insulin Glargine
n=11 Participants
Insulin glargine administered SC daily
|
|---|---|---|
|
Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)
High Dose Insulin
|
52.756 µmol/kg/min
Standard Deviation 11.862
|
56.321 µmol/kg/min
Standard Deviation 10.697
|
|
Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)
Low Dose Insulin
|
13.908 µmol/kg/min
Standard Deviation 13.181
|
18.765 µmol/kg/min
Standard Deviation 8.293
|
SECONDARY outcome
Timeframe: Day 29: Pre-breakfast, and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfastPopulation: All participants who received at least 1 dose of study drug and had evaluable PK data.
Outcome measures
| Measure |
Insulin Peglispro (LY2605541)
n=27 Participants
Insulin peglispro (LY2605541) administered SC daily
|
Insulin Glargine
n=24 Participants
Insulin glargine administered SC daily
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Last Time (AUC [0 Tlast]) for Paracetamol
|
33400 ng*hr/mL
Geometric Coefficient of Variation 19
|
33600 ng*hr/mL
Geometric Coefficient of Variation 22
|
SECONDARY outcome
Timeframe: Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfastPopulation: All participants who received at least 1 dose of study drug and had VAS score.
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.
Outcome measures
| Measure |
Insulin Peglispro (LY2605541)
n=27 Participants
Insulin peglispro (LY2605541) administered SC daily
|
Insulin Glargine
n=27 Participants
Insulin glargine administered SC daily
|
|---|---|---|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Day 29: Hunger, 5 hours post breakfast
|
53.8 millimeters (mm)
Standard Deviation 27.9
|
58.9 millimeters (mm)
Standard Deviation 24.6
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Day 29: Food amount, waking
|
32.5 millimeters (mm)
Standard Deviation 20.6
|
37.7 millimeters (mm)
Standard Deviation 22.8
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Day 29: Food amount, 5 hours post-breakfast
|
31.8 millimeters (mm)
Standard Deviation 20.1
|
38.1 millimeters (mm)
Standard Deviation 21.8
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Day 29: Hunger, waking
|
27.1 millimeters (mm)
Standard Deviation 22.1
|
32.1 millimeters (mm)
Standard Deviation 26.5
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 25%: Hunger, waking
|
27.5 millimeters (mm)
Standard Deviation 30.4
|
35.8 millimeters (mm)
Standard Deviation 28.5
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 25%: Hunger, 5 hours post breakfast
|
56.1 millimeters (mm)
Standard Deviation 30.7
|
58.0 millimeters (mm)
Standard Deviation 26.2
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 25%: Food amount, waking
|
30.8 millimeters (mm)
Standard Deviation 28.9
|
36.4 millimeters (mm)
Standard Deviation 27.6
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 25%: Food amount, 5 hours post-breakfast
|
56.5 millimeters (mm)
Standard Deviation 28.0
|
59.0 millimeters (mm)
Standard Deviation 24.9
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 50%: Hunger, waking
|
36.0 millimeters (mm)
Standard Deviation 26.2
|
28.2 millimeters (mm)
Standard Deviation 21.9
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 50%: Hunger, 5 hours post breakfast
|
56.5 millimeters (mm)
Standard Deviation 26.7
|
64.0 millimeters (mm)
Standard Deviation 25.0
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 50%: Food amount, waking
|
37.1 millimeters (mm)
Standard Deviation 25.2
|
31.7 millimeters (mm)
Standard Deviation 21.9
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 50%: Food amount, 5 hours post-breakfast
|
55.0 millimeters (mm)
Standard Deviation 24.8
|
64.2 millimeters (mm)
Standard Deviation 23.5
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 75%: Hunger, waking
|
29.8 millimeters (mm)
Standard Deviation 25.4
|
30.9 millimeters (mm)
Standard Deviation 27.5
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 75%: Hunger, 5 hours post breakfast
|
55.5 millimeters (mm)
Standard Deviation 27.7
|
62.5 millimeters (mm)
Standard Deviation 25.3
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 75%: Food amount, waking
|
32.6 millimeters (mm)
Standard Deviation 24.6
|
31.4 millimeters (mm)
Standard Deviation 55.3
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 75%: Food amount, 5 hours post-breakfast
|
57.0 millimeters (mm)
Standard Deviation 27.1
|
62.2 millimeters (mm)
Standard Deviation 24.0
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 100%: Hunger, waking
|
28.9 millimeters (mm)
Standard Deviation 22.9
|
29.6 millimeters (mm)
Standard Deviation 24.3
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 100%: Hunger, 5 hours post breakfast
|
55.0 millimeters (mm)
Standard Deviation 30.2
|
59.0 millimeters (mm)
Standard Deviation 26.9
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 100%: Food amount, waking
|
32.3 millimeters (mm)
Standard Deviation 22.9
|
35.7 millimeters (mm)
Standard Deviation 23.7
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 100%: Food amount, 5 hours post-breakfast
|
55.3 millimeters (mm)
Standard Deviation 29.1
|
58.6 millimeters (mm)
Standard Deviation 26.4
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 150%: Hunger, waking
|
31.4 millimeters (mm)
Standard Deviation 20.4
|
28.5 millimeters (mm)
Standard Deviation 16.9
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 150%: Hunger, 5 hours post breakfast
|
52.2 millimeters (mm)
Standard Deviation 27.7
|
58.6 millimeters (mm)
Standard Deviation 28.4
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 150%: Food amount, waking
|
34.3 millimeters (mm)
Standard Deviation 17.6
|
34.1 millimeters (mm)
Standard Deviation 17.1
|
|
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
Overall 150%: Food amount, 5 hours post-breakfast
|
52.7 millimeters (mm)
Standard Deviation 25.9
|
58.3 millimeters (mm)
Standard Deviation 26.1
|
SECONDARY outcome
Timeframe: Day 29, predose and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfastPopulation: All participants who received at least 1 dose of study drug and had evaluable PD data.
Outcome measures
| Measure |
Insulin Peglispro (LY2605541)
n=27 Participants
Insulin peglispro (LY2605541) administered SC daily
|
Insulin Glargine
n=27 Participants
Insulin glargine administered SC daily
|
|---|---|---|
|
Pharmacodynamics (PD): Area Under the Concentration Zero Through 5 Hours (AUC 0-5h) for Triglycerides
|
6.85 ng*hr/mL
Standard Deviation 3.13
|
6.01 ng*hr/mL
Standard Deviation 2.22
|
SECONDARY outcome
Timeframe: Day 35, insulin clearance during lispro infusion (dosing=infusion)Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
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.
Outcome measures
| Measure |
Insulin Peglispro (LY2605541)
n=27 Participants
Insulin peglispro (LY2605541) administered SC daily
|
Insulin Glargine
n=25 Participants
Insulin glargine administered SC daily
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp
Clamp Period 1-3 Hours
|
243 pmol* hr/L
Standard Deviation 78.9
|
222 pmol* hr/L
Standard Deviation 84.7
|
|
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp
Clamp Period 4-6 Hours
|
926 pmol* hr/L
Standard Deviation 335
|
897 pmol* hr/L
Standard Deviation 333
|
Adverse Events
Insulin Peglispro (LY2605541, With Insulin Lispro)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Insulin Glargine (With Insulin Lispro)
Serious events: 2 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Insulin Peglispro (LY2605541, With Insulin Lispro)
n=27 participants at risk
Insulin peglispro (LY2605541) once daily subcutaneous (SC) injection at bedtime. Insulin lispro given SC prandially or as bolus as required
|
Insulin Glargine (With Insulin Lispro)
n=28 participants at risk
Insulin glargine once daily SC injection at bedtime. Insulin lispro given SC prandially or as a bolus as required
|
|---|---|---|
|
Infections and infestations
Viral infection
|
0.00%
0/27
All randomized participants.
|
3.6%
1/28 • Number of events 1
All randomized participants.
|
|
Nervous system disorders
Neuralgic amyotrophy
|
0.00%
0/27
All randomized participants.
|
3.6%
1/28 • Number of events 1
All randomized participants.
|
Other adverse events
| Measure |
Insulin Peglispro (LY2605541, With Insulin Lispro)
n=27 participants at risk
Insulin peglispro (LY2605541) once daily subcutaneous (SC) injection at bedtime. Insulin lispro given SC prandially or as bolus as required
|
Insulin Glargine (With Insulin Lispro)
n=28 participants at risk
Insulin glargine once daily SC injection at bedtime. Insulin lispro given SC prandially or as a bolus as required
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/27
All randomized participants.
|
7.1%
2/28 • Number of events 2
All randomized participants.
|
|
General disorders
Fatigue
|
7.4%
2/27 • Number of events 2
All randomized participants.
|
0.00%
0/28
All randomized participants.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/27
All randomized participants.
|
7.1%
2/28 • Number of events 2
All randomized participants.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.4%
2/27 • Number of events 2
All randomized participants.
|
0.00%
0/28
All randomized participants.
|
|
Nervous system disorders
Headache
|
14.8%
4/27 • Number of events 7
All randomized participants.
|
14.3%
4/28 • Number of events 4
All randomized participants.
|
|
Vascular disorders
Phlebitis
|
7.4%
2/27 • Number of events 2
All randomized participants.
|
7.1%
2/28 • Number of events 2
All randomized participants.
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60