A Study to Compare the Effects of a Test and Reference Formulation of LY900014 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02752087
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Days): 30
• Patients Per Site Per Month: 24.4

Study Details

Study Description

Brief Summary

This study of healthy participants evaluated the concentration of a test LY900014 and a reference LY900014 formulation in the bloodstream and how it affected the blood sugar levels. The whole study, including screening, took up to 8 weeks to complete.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: LY900014	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Study to Compare the Pharmacokinetics and Pharmacodynamics of LY900014 Test Versus Reference Formulations in Healthy Subjects
• Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: U-193 LY900014 Test LY900014 test dose administered via subcutaneous (SC) injection	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Active Comparator: U-95 LY900014 Reference LY900014 reference dose administered via SC injection	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 8 Hours (AUC[0-8 Hours]) [5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, 420, and 480 minutes post study dose for each treatment]

   PK: Insulin Lispro Area Under the Concentration Curve From Time Zero to 8 Hours (AUC[0-8 Hours])

Secondary Outcome Measures

1. Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot) [Blood glucose was measured approximately every 2.5 minutes for the first 30 minutes, then every 5 minutes until 120 minutes post dose, and then every 10 minutes until 480 minutes post dose]

   Gtot is the total glucose infusion over the clamp duration. It is used to measure the study drug action over time as measured by the euglycemic clamp procedure.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Female participants who can potentially get pregnant:

• Must have a negative pregnancy test at the time of screening

• Agree to continue to use a reliable method of birth control until the end of the study

• Have a body mass index (BMI) of 18.0 to 30.0 kilogram per meter square (kg/m²), inclusive, at screening

• Are nonsmokers, have not smoked for at least 2 months before entering the study

Exclusion Criteria:

• Are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study

• Have known allergies to insulin lispro, related compounds, or any components of the formulation

• Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs

• Intend to use over-the-counter or prescription medication within 7 and 14 days, respectively, before dosing (apart from vitamin/mineral supplements, occasional paracetamol, hormonal contraception, or thyroid-replacement therapy)

• Have used systemic glucocorticoids within 3 months prior to entry into the study

• Have donated blood of more than 450 milliliters (mL) or more in the last 3 months or provided any blood donation within the last month before screening

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)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02752087
• Other Study ID Numbers: 16489; I8B-MC-ITRP
• First Posted: Apr 26, 2016
• Last Update Posted: May 1, 2020
• Last Verified: Jun 1, 2016

Study Results

Participant Flow

Recruitment Details	This was a four-period crossover study of U-193 LY900014 test formulation and U-95 LY900014 reference formulation with a minimum of 3 days between dosing.

Arm/Group Title	LY900014 Test/Reference/Test/Reference	LY900014 Reference/Test/Reference/Test
Arm/Group Description	U-193 LY900014 test formulation administered once subcutaneously (SC) in Study Periods 1 and 3. U-95 LY900014 reference formulation administered once SC in Study Periods 2 and 4.	U-95 LY900014 reference formulation administered once SC in study periods 1 and 3. U-193 LY900014 test formulation administered once SC in study periods 2 and 4.
Period Title: Study Period 1
STARTED	12	12
Received Study Drug	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: Study Period 1
STARTED	12	12
COMPLETED	11	12
NOT COMPLETED	1	0
Period Title: Study Period 1
STARTED	11	12
Received Study Drug	11	12
COMPLETED	11	12
NOT COMPLETED	0	0
Period Title: Study Period 1
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0
Period Title: Study Period 1
STARTED	11	12
Received Study Drug	11	12
COMPLETED	11	12
NOT COMPLETED	0	0
Period Title: Study Period 1
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0
Period Title: Study Period 1
STARTED	11	12
Received Study Drug	11	12
COMPLETED	11	12
NOT COMPLETED	0	0
Period Title: Study Period 1
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	U-193 LY900014 test formulation administered once SC in 2 of 4 study periods. U-95 LY900014 reference formulation administered once SC in 2 of 4 study periods.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.7 (7.2)
Sex: Female, Male (Count of Participants)
Female	2 8.3%
Male	22 91.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	24 100%
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	24 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 8 Hours (AUC[0-8 Hours])
Description	PK: Insulin Lispro Area Under the Concentration Curve From Time Zero to 8 Hours (AUC[0-8 Hours])
Time Frame	5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, 420, and 480 minutes post study dose for each treatment

Outcome Measure Data

Analysis Population Description

All participants who completed at least 1 study period and had measurable insulin lispro concentrations.

Arm/Group Title	LY900014 Reference	LY900014 Test
Arm/Group Description	U-95 LY900014 reference formulation administered once SC in 2 of 4 study periods.	U-193 LY900014 test formulation administered once SC in 2 of 4 study periods.
Measure Participants	23	24
Measure Number of observations	46	47
Geometric Mean (Geometric Coefficient of Variation) [picomole*hour/liter (pmol*h/L)]	2440 (13)	2430 (13)

2. Secondary Outcome

Title	Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot)
Description	Gtot is the total glucose infusion over the clamp duration. It is used to measure the study drug action over time as measured by the euglycemic clamp procedure.
Time Frame	Blood glucose was measured approximately every 2.5 minutes for the first 30 minutes, then every 5 minutes until 120 minutes post dose, and then every 10 minutes until 480 minutes post dose

Outcome Measure Data

Analysis Population Description

All participants who completed at least 1 clamp procedure.

Arm/Group Title	LY900014 Reference	LY900014 Test
Arm/Group Description	U-95 LY900014 reference formulation administered once SC in 2 of 4 study periods.	U-193 LY900014 test formulation administered once SC in 2 of 4 study periods.
Measure Participants	23	24
Measure Number of observations	46	47
Geometric Mean (Geometric Coefficient of Variation) [milligram (mg)]	108,000 (34)	117,000 (35)

Adverse Events

Arm/Group Title	LY900014 Test		LY900014 Reference
Arm/Group Description	U-193 LY900014 test formulation administered once SC in 2 of 4 study periods.		U-95 LY900014 reference formulation administered once SC in 2 of 4 study periods.
All Cause Mortality
	LY900014 Test		LY900014 Reference
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LY900014 Test		LY900014 Reference
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	LY900014 Test		LY900014 Reference
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/24 (37.5%)		8/23 (34.8%)
General disorders
Infusion site erythema	2/24 (8.3%)	2	0/23 (0%)	0
Infusion site swelling	3/24 (12.5%)	5	3/23 (13%)	3
Injection site erythema	1/24 (4.2%)	1	2/23 (8.7%)	3
Injection site pain	2/24 (8.3%)	2	3/23 (13%)	3
Vessel puncture site bruise	5/24 (20.8%)	9	1/23 (4.3%)	1
Vessel puncture site rash	2/24 (8.3%)	5	1/23 (4.3%)	2

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.