Study to Compare 2 Formulations of LY900014 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03616977
• Collaborator: (none)
• Enrollment: 69
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.5
• Patients Per Site Per Month: 27.3

Study Details

Study Description

Brief Summary

The study involves a comparison of 2 formulations of LY900014, which is a type of fast acting insulin. Study participants will be administered LY900014 U-100 two times and LY900014 U-200 two times, over 4 study periods, by injection under the skin. Blood samples will be taken to compare how the body handles the study drugs and how they affect the blood sugar levels. Side effects and tolerability will be documented. The study will last about 4 weeks, not including screening and follow up. Screening is required within 28 days prior to the start of the study and follow up is required at least 2 weeks after the last dose of study drug.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: LY900014 U-200; Drug: LY900014 U-100	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Bioequivalence Study Comparing 2 Formulations of LY900014 in Healthy Subjects
• Actual Study Start Date: Aug 3, 2018
• Actual Primary Completion Date: Oct 19, 2018
• Actual Study Completion Date: Oct 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 U-200 Single subcutaneous (SC) dose of LY900014 U-200 in two of four study periods.	Drug: LY900014 U-200; Administered SC; Other Names: Ultra-Rapid Lispro
Experimental: LY900014 U-100 Single SC dose of LY900014 U-100 in two of four study periods.	Drug: LY900014 U-100; Administered SC; Other Names: Ultra-Rapid Lispro

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours(h) (AUC [0-10h]) Following Administration of Each Study Arm [Period 1 through 4 Day 1: Predose, 5 minutes(m),10m,15m, 20m, 25m, 30m, 35m, 40m, 45m, 50m, 55m, 60m, 70m, 90m, 120m,150m,180m, 240m, 300m, 360m, 420m, 480m, 540m, and 600m postdose]

   Pharmacokinetics (PK): Insulin Lispro AUC time zero to 10 hours.

Secondary Outcome Measures

1. Glucodynamics (GD): Total Amount of Glucose Infused (Gtot) Over Duration of Clamp Following Administration of Each Study Arm [Period 1 through 4 Day 1: Predose, every 10 minutes(m) for 30m prior to dosing; During clamp: every 2.5m for 30m; every 5m for 30 to 120m; every 10m for 120 to 480m, and every 20m for 480m to 600m postdose]

   GD: 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 study treatment by adjusting the exogenous glucose infusion rate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 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

• Have veins suitable for easy blood collection and glucose solution infusion

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

• Had donated blood of more than 450 milliliters (mL) or participated in a clinical trial with similar blood loss within the last 3 months

• Have a regular alcohol intake greater than 21 units/week (male), or 14 units/week (female)

• Smoke more than 10 cigarettes per day

• Are infected with hepatitis B or human immunodeficiency virus (HIV)

• Are taking illegal drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lilly Centre for Clinical Pharmacology	Singapore		Singapore	138623

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 20, 2018
• Statistical Analysis Plan - Oct 12, 2018

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03616977
• Other Study ID Numbers: 17152; I8B-MC-ITSS
• First Posted: Aug 6, 2018
• Last Update Posted: Apr 30, 2020
• Last Verified: Nov 1, 2018

• 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: Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	Sequence 1	Sequence 2
Arm/Group Description	Single SC dose of LY900014 U-200 in Periods 1 and 3. Single SC dose of LY900014 U-100 in Periods 2 and 4.	Single SC dose of LY900014 U-100 in Periods 1 and 3. Single SC dose of LY900014 U-200 in Periods 2 and 4.
Period Title: Period 1
STARTED	34	35
Received at Least One Dose of Study Drug	34	34
COMPLETED	34	34
NOT COMPLETED	0	1
Period Title: Period 1
STARTED	34	34
COMPLETED	34	34
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	34	33
Received Study Drug	33	32
COMPLETED	33	32
NOT COMPLETED	1	1
Period Title: Period 1
STARTED	33	32
COMPLETED	33	32
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	Single subcutaneous (SC) dose of LY900014 U-200 in two of four study periods. Single SC dose of LY900014 U-100 in two of four study periods.
Overall Participants	68
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	67 98.5%
>=65 years	1 1.5%
Sex: Female, Male (Count of Participants)
Female	3 4.4%
Male	65 95.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	68 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	67 98.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	1 1.5%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Singapore	68 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours(h) (AUC [0-10h]) Following Administration of Each Study Arm
Description	Pharmacokinetics (PK): Insulin Lispro AUC time zero to 10 hours.
Time Frame	Period 1 through 4 Day 1: Predose, 5 minutes(m),10m,15m, 20m, 25m, 30m, 35m, 40m, 45m, 50m, 55m, 60m, 70m, 90m, 120m,150m,180m, 240m, 300m, 360m, 420m, 480m, 540m, and 600m postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	LY900014 U-100	LY900014 U-200
Arm/Group Description	Single SC dose of LY900014 U-100 in two of four study periods. LY900014 U-100: Administered SC	Single subcutaneous (SC) dose of LY900014 U-200 in two of four study periods. LY900014 U-200: Administered SC
Measure Participants	68	68
Geometric Mean (Geometric Coefficient of Variation) [picomole times hour per liter (pmol*h/L)]	1690 (18)	1710 (17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014 U-100, LY900014 U-200
	Comments
	Type of Statistical Test	Equivalence
	Comments	Bioequivalence will be concluded if the 2-sided 90% Confidence Interval is completely contained within the interval (0.80, 1.25).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least squares means
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 90%; 0.961 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Glucodynamics (GD): Total Amount of Glucose Infused (Gtot) Over Duration of Clamp Following Administration of Each Study Arm
Description	GD: 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 study treatment by adjusting the exogenous glucose infusion rate.
Time Frame	Period 1 through 4 Day 1: Predose, every 10 minutes(m) for 30m prior to dosing; During clamp: every 2.5m for 30m; every 5m for 30 to 120m; every 10m for 120 to 480m, and every 20m for 480m to 600m postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and have evaluable glucodynamic data.

Arm/Group Title	LY900014 U-100	LY900014 U-200
Arm/Group Description	Single SC dose of LY900014 U-100 in two of four study periods. LY900014 U-100: Administered SC	Single SC dose of LY900014 U-200 in two of four study periods. LY900014 U-200: Administered SC
Measure Participants	68	68
Geometric Mean (Geometric Coefficient of Variation) [milligram per kilogram (mg/kg)]	1530 (46)	1620 (45)

Adverse Events

Time Frame	Baseline to end of study (Up to 62 days)
Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	LY900014 U-100		LY900014 U-200
Arm/Group Description	Single SC dose of LY900014 U-100.		Single SC dose of LY900014 U-200.
All Cause Mortality
	LY900014 U-100		LY900014 U-200
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/68 (0%)
Serious Adverse Events
	LY900014 U-100		LY900014 U-200
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/68 (0%)
Other (Not Including Serious) Adverse Events
	LY900014 U-100		LY900014 U-200
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/68 (29.4%)		19/68 (27.9%)
General disorders
Catheter site swelling	4/68 (5.9%)	5	0/68 (0%)	0
Infusion site pain	4/68 (5.9%)	4	3/68 (4.4%)	4
Infusion site swelling	10/68 (14.7%)	10	10/68 (14.7%)	10
Nervous system disorders
Headache	7/68 (10.3%)	8	7/68 (10.3%)	10

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.