Trial Outcomes & Findings for A Study of LY900014 in Participants With Type 2 Diabetes on Insulin Injection Therapy (NCT NCT02703337)
NCT ID: NCT02703337
Last Updated: 2020-06-17
Results Overview
PK: Insulin Lispro AUC(0-5h) (Part A)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
Day 1: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment
Results posted on
2020-06-17
Participant Flow
Two-part study compared individualized doses of LY900014 (Test) to insulin lispro (Reference). Part A: LY900014 or insulin lispro once subcutaneously (SC) before, at, or after start of meal in each of 6 periods. Minimum 1 day washout. Part B: LY900014 or insulin lispro SC before meals for 14 days. Participants were expected to complete both parts.
Participant milestones
| Measure |
Part A Sequence 1, ABFCED
A = LY900014 Test (15 minutes \[mins\] before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 2, BCADFE
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 3, CDBEAF
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 4, DECFBA
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 5, EFDACB
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 6, FAEBDC
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part B LY900014 (Test)
Individualized doses of LY900014 Test administered SC immediately before meals for 14 days.
|
Part B Insulin Lispro (Reference)
Individualized doses of Insulin Lispro Reference administered SC immediately before meals for 14 days.
|
|---|---|---|---|---|---|---|---|---|
|
Period One (Part A)
STARTED
|
5
|
5
|
5
|
5
|
5
|
5
|
0
|
0
|
|
Period One (Part A)
Received Study Drug
|
5
|
5
|
5
|
5
|
5
|
5
|
0
|
0
|
|
Period One (Part A)
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period One (Part A)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Period Two (Part A)
STARTED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Two (Part A)
Received Study Drug
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Two (Part A)
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Two (Part A)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period Three (Part A)
STARTED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Three (Part A)
Received Study Drug
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Three (Part A)
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Three (Part A)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period Four (Part A)
STARTED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Four (Part A)
Received Study Drug
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Four (Part A)
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Four (Part A)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period Five (Part A)
STARTED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Five (Part A)
Received Study Drug
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Five (Part A)
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Five (Part A)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period Six (Part A)
STARTED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Six (Part A)
Received Study Drug
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Six (Part A)
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
5
|
0
|
0
|
|
Period Six (Part A)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part B
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
15
|
14
|
|
Part B
Received Study Drug
|
0
|
0
|
0
|
0
|
0
|
0
|
15
|
14
|
|
Part B
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
15
|
14
|
|
Part B
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Part A Sequence 1, ABFCED
A = LY900014 Test (15 minutes \[mins\] before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 2, BCADFE
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 3, CDBEAF
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 4, DECFBA
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 5, EFDACB
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part A Sequence 6, FAEBDC
A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).
|
Part B LY900014 (Test)
Individualized doses of LY900014 Test administered SC immediately before meals for 14 days.
|
Part B Insulin Lispro (Reference)
Individualized doses of Insulin Lispro Reference administered SC immediately before meals for 14 days.
|
|---|---|---|---|---|---|---|---|---|
|
Period One (Part A)
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Study of LY900014 in Participants With Type 2 Diabetes on Insulin Injection Therapy
Baseline characteristics by cohort
| Measure |
All Participants
n=30 Participants
Individualized doses of LY900014 (Test) or insulin lispro (Reference) administered once SC at various mealtime intervals in each of six periods (Part A) and immediately before meals for 14 days (Part B).
|
|---|---|
|
Age, Continuous
|
58.9 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
30 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
|
30 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
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatmentPopulation: All participants in Part A who received study drug and had evaluable PK data. For one participant in the LY900014 - Test (Part A) group, the insulin lispro PK profile (period two) was excluded from the mean PK analysis, as there was no absorption phase observed.
PK: Insulin Lispro AUC(0-5h) (Part A)
Outcome measures
| Measure |
Insulin Lispro - Reference (Part A)
n=29 Participants
Individualized doses of insulin lispro (Reference) administered once SC in three of six periods.
|
LY900014 - Test (Part A)
n=29 Participants
Individualized doses of LY900014 (Test) administered once SC in three of six periods.
|
|---|---|---|
|
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part A)
|
1520 picomole*hour per liter (pmol*h/L)
Geometric Coefficient of Variation 62
|
1830 picomole*hour per liter (pmol*h/L)
Geometric Coefficient of Variation 68
|
PRIMARY outcome
Timeframe: Days 1 and 14: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatmentPopulation: All participants in Part B who received study drug and had evaluable PK data.
PK: Insulin Lispro AUC(0-5h) (Part B)
Outcome measures
| Measure |
Insulin Lispro - Reference (Part A)
n=14 Participants
Individualized doses of insulin lispro (Reference) administered once SC in three of six periods.
|
LY900014 - Test (Part A)
n=15 Participants
Individualized doses of LY900014 (Test) administered once SC in three of six periods.
|
|---|---|---|
|
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B)
Day 1
|
1390 pmol*h/L
Geometric Coefficient of Variation 86
|
1900 pmol*h/L
Geometric Coefficient of Variation 59
|
|
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B)
Day 14
|
1450 pmol*h/L
Geometric Coefficient of Variation 76
|
1930 pmol*h/L
Geometric Coefficient of Variation 69
|
SECONDARY outcome
Timeframe: Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutesPopulation: All participants in Part A who received study drug immediately before a meal (0 min) and had evaluable PD data. Data were excluded if the participant did not keep identical insulin lispro dose during the MMTT assessments, did not complete the entire test meal, or had significant changes in nutrient consumption of the test meal.
PD: AUC(0-5h) of Glucose Relative to a MMTT (Part A)
Outcome measures
| Measure |
Insulin Lispro - Reference (Part A)
n=29 Participants
Individualized doses of insulin lispro (Reference) administered once SC in three of six periods.
|
LY900014 - Test (Part A)
n=28 Participants
Individualized doses of LY900014 (Test) administered once SC in three of six periods.
|
|---|---|---|
|
Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part A)
|
524 milligram*hour/deciliter (mg*h/dL)
Standard Deviation 146
|
395 milligram*hour/deciliter (mg*h/dL)
Standard Deviation 124
|
SECONDARY outcome
Timeframe: Days 1 and 14: Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes in each study periodPopulation: All participants in Part B who received study drug and had evaluable PD data. Data were excluded if the participant did not keep identical insulin lispro dose during the MMTT assessments, did not complete the entire test meal, or had significant changes in nutrient consumption of the test meal.
PD: AUC(0-5h) of Glucose Relative to a MMTT (Part B)
Outcome measures
| Measure |
Insulin Lispro - Reference (Part A)
n=14 Participants
Individualized doses of insulin lispro (Reference) administered once SC in three of six periods.
|
LY900014 - Test (Part A)
n=15 Participants
Individualized doses of LY900014 (Test) administered once SC in three of six periods.
|
|---|---|---|
|
Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B)
Day 1
|
439 mg*h/dL
Standard Deviation 104
|
407 mg*h/dL
Standard Deviation 163
|
|
Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B)
Day 14
|
453 mg*h/dL
Standard Deviation 133
|
387 mg*h/dL
Standard Deviation 151
|
Adverse Events
Insulin Lispro - Reference -15 Min (Part A)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Insulin Lispro - Reference 0 Min (Part A)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Insulin Lispro - Reference +15 Min (Part A)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
LY900014 - Test -15 Min (Part A)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
LY900014 - Test 0 Min (Part A)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
LY900014 - Test +15 Min (Part A)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Insulin Lispro Open Label - (Part A)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Insulin Lispro - Reference (Part B)
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
LY900014 - Test (Part B)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Insulin Lispro Open Label - (Part B)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Insulin Lispro - Reference -15 Min (Part A)
n=29 participants at risk
Individualized doses of insulin lispro (Reference) administered once SC 15 minutes prior to meal in one of six periods.
|
Insulin Lispro - Reference 0 Min (Part A)
n=30 participants at risk
Individualized doses of insulin lispro (Reference) administered once SC immediately before meal in one of six periods.
|
Insulin Lispro - Reference +15 Min (Part A)
n=29 participants at risk
Individualized doses of insulin lispro (Reference) administered once SC 15 minutes after start of meal in one of six periods.
|
LY900014 - Test -15 Min (Part A)
n=29 participants at risk
Individualized doses of LY900014 (Test) administered once SC 15 minutes prior to meal in one of six periods.
|
LY900014 - Test 0 Min (Part A)
n=29 participants at risk
Individualized doses of LY900014 (Test) administered once SC immediately before meal in one of six periods.
|
LY900014 - Test +15 Min (Part A)
n=29 participants at risk
Individualized doses of LY900014 (Test) administered once SC 15 minutes after start of meal in one of six periods.
|
Insulin Lispro Open Label - (Part A)
n=30 participants at risk
Individualized doses of insulin lispro administered SC between periods.
|
Insulin Lispro - Reference (Part B)
n=14 participants at risk
Individualized doses of insulin lispro (Reference) administered SC immediately before meals for 14 days.
|
LY900014 - Test (Part B)
n=15 participants at risk
Individualized doses of LY900014 (Test) administered SC immediately before meals for 14 days.
|
Insulin Lispro Open Label - (Part B)
n=27 participants at risk
Individualized doses of insulin lispro administered SC immediately before meals.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
General disorders
Pyrexia
|
0.00%
0/29
|
0.00%
0/30
|
0.00%
0/29
|
0.00%
0/29
|
0.00%
0/29
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14 • Number of events 1
|
0.00%
0/15
|
0.00%
0/27
|
Other adverse events
| Measure |
Insulin Lispro - Reference -15 Min (Part A)
n=29 participants at risk
Individualized doses of insulin lispro (Reference) administered once SC 15 minutes prior to meal in one of six periods.
|
Insulin Lispro - Reference 0 Min (Part A)
n=30 participants at risk
Individualized doses of insulin lispro (Reference) administered once SC immediately before meal in one of six periods.
|
Insulin Lispro - Reference +15 Min (Part A)
n=29 participants at risk
Individualized doses of insulin lispro (Reference) administered once SC 15 minutes after start of meal in one of six periods.
|
LY900014 - Test -15 Min (Part A)
n=29 participants at risk
Individualized doses of LY900014 (Test) administered once SC 15 minutes prior to meal in one of six periods.
|
LY900014 - Test 0 Min (Part A)
n=29 participants at risk
Individualized doses of LY900014 (Test) administered once SC immediately before meal in one of six periods.
|
LY900014 - Test +15 Min (Part A)
n=29 participants at risk
Individualized doses of LY900014 (Test) administered once SC 15 minutes after start of meal in one of six periods.
|
Insulin Lispro Open Label - (Part A)
n=30 participants at risk
Individualized doses of insulin lispro administered SC between periods.
|
Insulin Lispro - Reference (Part B)
n=14 participants at risk
Individualized doses of insulin lispro (Reference) administered SC immediately before meals for 14 days.
|
LY900014 - Test (Part B)
n=15 participants at risk
Individualized doses of LY900014 (Test) administered SC immediately before meals for 14 days.
|
Insulin Lispro Open Label - (Part B)
n=27 participants at risk
Individualized doses of insulin lispro administered SC immediately before meals.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/29
|
0.00%
0/30
|
0.00%
0/29
|
0.00%
0/29
|
0.00%
0/29
|
0.00%
0/29
|
13.3%
4/30 • Number of events 5
|
0.00%
0/14
|
0.00%
0/15
|
0.00%
0/27
|
|
Nervous system disorders
Headache
|
0.00%
0/29
|
0.00%
0/30
|
3.4%
1/29 • Number of events 1
|
0.00%
0/29
|
0.00%
0/29
|
0.00%
0/29
|
6.7%
2/30 • Number of events 3
|
0.00%
0/14
|
6.7%
1/15 • Number of events 1
|
0.00%
0/27
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/29
|
0.00%
0/30
|
0.00%
0/29
|
6.9%
2/29 • Number of events 2
|
10.3%
3/29 • Number of events 3
|
0.00%
0/29
|
0.00%
0/30
|
0.00%
0/14
|
0.00%
0/15
|
0.00%
0/27
|
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