Trial Outcomes & Findings for A Study of LY900014 Formulation at Different Injection Sites in Healthy Participants (NCT NCT03232983)
NCT ID: NCT03232983
Last Updated: 2020-04-30
Results Overview
Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose \[AUC(0-10h)\].
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
Day 1: Pre-dose, 2.5, 5, 10, 15, 20, 25, 30, 40, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose
Results posted on
2020-04-30
Participant Flow
This is an open-label, randomized, crossover, up to 10-hour euglycemic clamp study in which participants were randomized into one of four treatment sequences. Participants received single doses of 15 units of LY900014 on 4 occasions (treatment Periods 1 through 4) with a wash-out period of at least 3 days between study drug administration.
Participant milestones
| Measure |
LY900014 Treatment Sequence 1: Abdomen,Thigh, Deltoid(Arm), IV
Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen in Period 1, Thigh in Period 2, Deltoid (Arm) in Period 3, and single 15-U intravenous (IV) bolus injection in Period 4.
|
LY900014 Treatment Sequence 2: Deltoid, Abdomen, IV, Thigh
Single dose of 15-U of LY900014 administered SC into the: Deltoid in Period 1, Abdomen in Period 2, single 15-U IV bolus injection in Period 3, and single 15-U SC administration into the Thigh in Period 4.
|
LY900014 Treatment Sequence 3: IV, Deltoid, Thigh, Abdomen
Single 15-U IV bolus injection of LY900014 administered in Period 1, single 15-U dose administered SC in the Deltoid in Period 2, Thigh in Period 3, and Abdomen in Period 4.
|
LY900014 Treatment Sequence 4: Thigh, IV, Abdomen, Deltoid
Single dose of 15-U of LY900014 administered SC in Thigh in Period 1, single 15-U IV bolus injection in Period 2, single dose of 15-U administered SC in the Abdomen in Period 3, and Deltoid in Period 4.
|
|---|---|---|---|---|
|
Period 1
STARTED
|
7
|
7
|
7
|
7
|
|
Period 1
Received at Least One Dose of Study Drug
|
7
|
7
|
7
|
7
|
|
Period 1
COMPLETED
|
7
|
7
|
6
|
7
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Washout Period 1
STARTED
|
7
|
7
|
6
|
7
|
|
Washout Period 1
COMPLETED
|
7
|
7
|
6
|
7
|
|
Washout Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
7
|
7
|
6
|
7
|
|
Period 2
COMPLETED
|
7
|
7
|
6
|
7
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Washout Period 2
STARTED
|
7
|
7
|
6
|
7
|
|
Washout Period 2
COMPLETED
|
7
|
7
|
5
|
6
|
|
Washout Period 2
NOT COMPLETED
|
0
|
0
|
1
|
1
|
|
Period 3
STARTED
|
7
|
7
|
5
|
6
|
|
Period 3
COMPLETED
|
7
|
7
|
5
|
6
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Washout Period 3
STARTED
|
7
|
7
|
5
|
6
|
|
Washout Period 3
COMPLETED
|
7
|
7
|
5
|
6
|
|
Washout Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
7
|
7
|
5
|
6
|
|
Period 4
COMPLETED
|
6
|
7
|
5
|
6
|
|
Period 4
NOT COMPLETED
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
LY900014 Treatment Sequence 1: Abdomen,Thigh, Deltoid(Arm), IV
Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen in Period 1, Thigh in Period 2, Deltoid (Arm) in Period 3, and single 15-U intravenous (IV) bolus injection in Period 4.
|
LY900014 Treatment Sequence 2: Deltoid, Abdomen, IV, Thigh
Single dose of 15-U of LY900014 administered SC into the: Deltoid in Period 1, Abdomen in Period 2, single 15-U IV bolus injection in Period 3, and single 15-U SC administration into the Thigh in Period 4.
|
LY900014 Treatment Sequence 3: IV, Deltoid, Thigh, Abdomen
Single 15-U IV bolus injection of LY900014 administered in Period 1, single 15-U dose administered SC in the Deltoid in Period 2, Thigh in Period 3, and Abdomen in Period 4.
|
LY900014 Treatment Sequence 4: Thigh, IV, Abdomen, Deltoid
Single dose of 15-U of LY900014 administered SC in Thigh in Period 1, single 15-U IV bolus injection in Period 2, single dose of 15-U administered SC in the Abdomen in Period 3, and Deltoid in Period 4.
|
|---|---|---|---|---|
|
Period 1
Physician Decision
|
0
|
0
|
1
|
0
|
|
Washout Period 2
Physician Decision
|
0
|
0
|
1
|
0
|
|
Washout Period 2
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
|
Period 4
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Study of LY900014 Formulation at Different Injection Sites in Healthy Participants
Baseline characteristics by cohort
| Measure |
Overall
n=28 Participants
Single 15-U dose of LY900014 administered in treatment Period 1- 4, as SC injection into the abdomen, the thigh, the deltoid or an IV bolus injection, per randomized treatment sequence.
|
|---|---|
|
Age, Continuous
|
39.8 years
STANDARD_DEVIATION 8.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 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
|
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
|
28 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
|
0 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
Singapore
|
28 Participants
n=5 Participants
|
|
Weight
|
70.11 kilograms (kg)
STANDARD_DEVIATION 10.48 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1: Pre-dose, 2.5, 5, 10, 15, 20, 25, 30, 40, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dosePopulation: All participants who have received at least one dose of study drug and have measurable insulin lispro concentrations and evaluable PK data.
Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose \[AUC(0-10h)\].
Outcome measures
| Measure |
LY900014 (SC Abdomen)
n=25 Participants
Single 15-U dose of LY900014 administered subcutaneously (SC) into the abdomen in one period.
|
LY900014 (SC Deltoid)
n=26 Participants
Single 15-U dose of LY900014 administered SC into the deltoid in one period.
|
LY900014 (IV)
n=27 Participants
Single 15-U injection IV bolus of LY900014 administered in one period.
|
LY900014 (SC Thigh)
n=26 Participants
Single 15-U dose of LY900014 administered SC into the thigh in one period.
|
|---|---|---|---|---|
|
Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration
|
1760 picomole * hour/Liter (pmol * hr/L)
Geometric Coefficient of Variation 20
|
1800 picomole * hour/Liter (pmol * hr/L)
Geometric Coefficient of Variation 16
|
2770 picomole * hour/Liter (pmol * hr/L)
Geometric Coefficient of Variation 22
|
1750 picomole * hour/Liter (pmol * hr/L)
Geometric Coefficient of Variation 19
|
SECONDARY outcome
Timeframe: Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 120 to 480 minutes and every 10 minutes for 480 to 600 minutes post-dosePopulation: All participants who have received at least one dose of study drug administered and have completed at least one clamp procedure. The IV treatment arm was needed only for PK as it served as the reference to determine the absolute bioavailability.
Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of LY900014 by adjusting the exogenous glucose infusion rate.
Outcome measures
| Measure |
LY900014 (SC Abdomen)
n=25 Participants
Single 15-U dose of LY900014 administered subcutaneously (SC) into the abdomen in one period.
|
LY900014 (SC Deltoid)
n=26 Participants
Single 15-U dose of LY900014 administered SC into the deltoid in one period.
|
LY900014 (IV)
n=26 Participants
Single 15-U injection IV bolus of LY900014 administered in one period.
|
LY900014 (SC Thigh)
Single 15-U dose of LY900014 administered SC into the thigh in one period.
|
|---|---|---|---|---|
|
Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure
|
1490 milligram per kilogram (mg/kg)
Geometric Coefficient of Variation 45
|
1630 milligram per kilogram (mg/kg)
Geometric Coefficient of Variation 50
|
1730 milligram per kilogram (mg/kg)
Geometric Coefficient of Variation 38
|
—
|
Adverse Events
15-U LY900014 Abdomen
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
15-U LY900014 Thigh
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
15-U LY900014 Deltoid
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
15-U LY900014 IV
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
15-U LY900014 Abdomen
n=25 participants at risk
Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen.
|
15-U LY900014 Thigh
n=26 participants at risk
Single dose of 15-U of LY900014 administered SC into the Thigh.
|
15-U LY900014 Deltoid
n=26 participants at risk
Single dose of 15-U of LY900014 administered SC into the Deltoid.
|
15-U LY900014 IV
n=28 participants at risk
Single 15-U LY900014 administered IV bolus injection.
|
|---|---|---|---|---|
|
General disorders
Application site erythema
|
4.0%
1/25 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/26 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
7.7%
2/26 • Number of events 3 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Catheter site bruise
|
8.0%
2/25 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
7.7%
2/26 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
7.7%
2/26 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Catheter site erythema
|
0.00%
0/25 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.8%
1/26 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
7.7%
2/26 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Catheter site pain
|
4.0%
1/25 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.8%
1/26 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.8%
1/26 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
10.7%
3/28 • Number of events 4 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Catheter site swelling
|
0.00%
0/25 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.8%
1/26 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.8%
1/26 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
7.1%
2/28 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Infusion site erythema
|
0.00%
0/25 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
7.7%
2/26 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/26 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Infusion site pain
|
12.0%
3/25 • Number of events 4 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/26 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.8%
1/26 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Infusion site swelling
|
0.00%
0/25 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
7.7%
2/26 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
7.7%
2/26 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Injection site pain
|
4.0%
1/25 • Number of events 1 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/26 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
11.5%
3/26 • Number of events 3 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Vessel puncture site bruise
|
8.0%
2/25 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/26 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/26 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
|
General disorders
Vessel puncture site pain
|
8.0%
2/25 • Number of events 2 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/26 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/26 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline to end of study (up to 49 days)
All participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place