A Study of LY900014 Formulation at Different Injection Sites in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03232983
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 4
• Actual Duration (Months): 2.9
• Patients Per Site Per Month: 9.8

Study Details

Study Description

Brief Summary

This study evaluates a new formulation of insulin lispro, LY900014, a drug that lowers blood sugar. It is administered by injection into the vein and under the skin of the abdomen, thigh and arm.

The study will be conducted in healthy people to investigate the effect of different injection sites on the amount of insulin lispro in the bloodstream.

Side effects and tolerability will be documented. The study will last for about 10 weeks for each participant, including screening and follow up. Screening is required within 28 days prior to entering the study.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: LY900014 (SC); Drug: LY900014 (IV)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of Injection Site on the Relative and Absolute Bioavailability of Single Dose of LY900014 in Healthy Subjects
• Actual Study Start Date: Aug 14, 2017
• Actual Primary Completion Date: Nov 9, 2017
• Actual Study Completion Date: Nov 9, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 (SC Abdomen) Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen in one period	Drug: LY900014 (SC); Administered SC; Other Names: Ultra-Rapid Lispro
Experimental: LY900014 (SC Thigh) Single dose of 15-U of LY900014 administered SC into the thigh in one period	Drug: LY900014 (SC); Administered SC; Other Names: Ultra-Rapid Lispro
Experimental: LY900014 (SC Arm) Single dose of 15-U of LY900014 administered SC into the arm (deltoid) in one period	Drug: LY900014 (SC); Administered SC; Other Names: Ultra-Rapid Lispro
Active Comparator: LY900014 (IV) Single dose of 15-U of LY900014 administered intravenously (IV) in one period	Drug: LY900014 (IV); Administered IV; Other Names: Ultra-Rapid Lispro

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration [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]

   Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose [AUC(0-10h)].

Secondary Outcome Measures

1. Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure [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-dose]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Overtly healthy male or a female (not pregnant and agreeable to take birth control measures until study completion)

• Have a body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m²)

• Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results that are acceptable for the study

• Are nonsmokers, have not smoked for at least 6 months prior to entering the study

Exclusion Criteria:

• Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study

• Have previously participated or withdrawn from this study

• Had blood loss of more than 450 milliliters (mL) within the last 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Singapore		Singapore	117597

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Jul 14, 2017
• Statistical Analysis Plan - Aug 4, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03232983
• Other Study ID Numbers: 16639; I8B-MC-ITRT
• First Posted: Jul 28, 2017
• Last Update Posted: Apr 30, 2020
• Last Verified: Dec 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Insulin Lispro

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	LY900014 Treatment Sequence 1: Abdomen,Thigh, Deltoid(Arm), IV	LY900014 Treatment Sequence 2: Deltoid, Abdomen, IV, Thigh	LY900014 Treatment Sequence 3: IV, Deltoid, Thigh, Abdomen	LY900014 Treatment Sequence 4: Thigh, IV, Abdomen, Deltoid
Arm/Group Description	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.	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.	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.	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 Title: Period 1
STARTED	7	7	7	7
Received at Least One Dose of Study Drug	7	7	7	7
COMPLETED	7	7	6	7
NOT COMPLETED	0	0	1	0
Period Title: Period 1
STARTED	7	7	6	7
COMPLETED	7	7	6	7
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	7	7	6	7
COMPLETED	7	7	6	7
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	7	7	6	7
COMPLETED	7	7	5	6
NOT COMPLETED	0	0	1	1
Period Title: Period 1
STARTED	7	7	5	6
COMPLETED	7	7	5	6
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	7	7	5	6
COMPLETED	7	7	5	6
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	7	7	5	6
COMPLETED	6	7	5	6
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	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.
Overall Participants	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.8 (8.6)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	28 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	28 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	28 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Singapore	28 100%
Weight (kilograms (kg)) [Geometric Mean (Standard Deviation) ]
Geometric Mean (Standard Deviation) [kilograms (kg)]	70.11 (10.48)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration
Description	Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose [AUC(0-10h)].
Time Frame	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

Outcome Measure Data

Analysis Population Description

All participants who have received at least one dose of study drug and have measurable insulin lispro concentrations and evaluable PK data.

Arm/Group Title	LY900014 (SC Abdomen)	LY900014 (SC Deltoid)	LY900014 (IV)	LY900014 (SC Thigh)
Arm/Group Description	Single 15-U dose of LY900014 administered subcutaneously (SC) into the abdomen in one period.	Single 15-U dose of LY900014 administered SC into the deltoid in one period.	Single 15-U injection IV bolus of LY900014 administered in one period.	Single 15-U dose of LY900014 administered SC into the thigh in one period.
Measure Participants	25	26	27	26
Geometric Mean (Geometric Coefficient of Variation) [picomole * hour/Liter (pmol * hr/L)]	1760 (20)	1800 (16)	2770 (22)	1750 (19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014 (SC Abdomen), LY900014 (SC Deltoid)
	Comments	Geometric Least Squares Means (LSMeans) were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Least Squares Means
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 90%; 0.992 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY900014 (SC Abdomen), LY900014 (SC Thigh)
	Comments	Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Least Squares Means
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 90%; 0.962 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure
Description	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.
Time Frame	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-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	LY900014 (SC Abdomen)	LY900014 (SC Deltoid)	LY900014 (SC Thigh)
Arm/Group Description	Single 15-U dose of LY900014 administered subcutaneously (SC) into the abdomen in one period.	Single 15-U dose of LY900014 administered SC into the arm in one period.	Single 15-U dose of LY900014 administered SC into the thigh in one period.
Measure Participants	25	26	26
Geometric Least Squares Mean (Geometric Coefficient of Variation) [milligram per kilogram (mg/kg)]	1490 (45)	1630 (50)	1730 (38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014 (SC Abdomen), LY900014 (SC Deltoid)
	Comments	Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 90%; 1.00 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY900014 (SC Abdomen), LY900014 (IV)
	Comments	Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 90%; 1.04 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Baseline to end of study (up to 49 days)
Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	15-U LY900014 Abdomen		15-U LY900014 Thigh		15-U LY900014 Deltoid		15-U LY900014 IV
Arm/Group Description	Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen.		Single dose of 15-U of LY900014 administered SC into the Thigh.		Single dose of 15-U of LY900014 administered SC into the Deltoid.		Single 15-U LY900014 administered IV bolus injection.
All Cause Mortality
	15-U LY900014 Abdomen		15-U LY900014 Thigh		15-U LY900014 Deltoid		15-U LY900014 IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/26 (0%)		0/26 (0%)		0/28 (0%)
Serious Adverse Events
	15-U LY900014 Abdomen		15-U LY900014 Thigh		15-U LY900014 Deltoid		15-U LY900014 IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/26 (0%)		0/26 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	15-U LY900014 Abdomen		15-U LY900014 Thigh		15-U LY900014 Deltoid		15-U LY900014 IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/25 (24%)		7/26 (26.9%)		11/26 (42.3%)		4/28 (14.3%)
General disorders
Application site erythema	1/25 (4%)	1	0/26 (0%)	0	2/26 (7.7%)	3	1/28 (3.6%)	2
Catheter site bruise	2/25 (8%)	2	2/26 (7.7%)	2	2/26 (7.7%)	2	1/28 (3.6%)	2
Catheter site erythema	0/25 (0%)	0	1/26 (3.8%)	1	2/26 (7.7%)	2	0/28 (0%)	0
Catheter site pain	1/25 (4%)	2	1/26 (3.8%)	1	1/26 (3.8%)	1	3/28 (10.7%)	4
Catheter site swelling	0/25 (0%)	0	1/26 (3.8%)	1	1/26 (3.8%)	1	2/28 (7.1%)	2
Infusion site erythema	0/25 (0%)	0	2/26 (7.7%)	2	0/26 (0%)	0	1/28 (3.6%)	1
Infusion site pain	3/25 (12%)	4	0/26 (0%)	0	1/26 (3.8%)	1	1/28 (3.6%)	1
Infusion site swelling	0/25 (0%)	0	2/26 (7.7%)	2	2/26 (7.7%)	2	1/28 (3.6%)	1
Injection site pain	1/25 (4%)	1	0/26 (0%)	0	3/26 (11.5%)	3	0/28 (0%)	0
Vessel puncture site bruise	2/25 (8%)	2	0/26 (0%)	0	0/26 (0%)	0	0/28 (0%)	0
Vessel puncture site pain	2/25 (8%)	2	0/26 (0%)	0	0/26 (0%)	0	0/28 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.