A Comparative Study of LY900014 With Insulin Lispro (Humalog) in Participants With Type 1 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03341299
• Collaborator: (none)
• Enrollment: 36
• Locations: 2
• Arms: 4
• Actual Duration (Months): 4.6
• Patients Per Site: 18
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate a new formulation of insulin lispro, LY900014, which is a drug that lowers blood sugar. The study will look at how the body processes LY900014, and the effect of LY900014 on blood sugar levels following a standard meal. For each participant, the study will consist of 4 periods and there will be approximately 12 weeks from screening to final study follow up.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Biological: LY900014; Biological: Insulin Lispro	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Study to Evaluate the Pharmacokinetics and Glucodynamics of LY900014 Compared to Humalog® in Patients With T1DM
• Actual Study Start Date: Nov 13, 2017
• Actual Primary Completion Date: Apr 3, 2018
• Actual Study Completion Date: Apr 3, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 Before Meal Individualized dose of LY900014 administered subcutaneously (SC) immediately before meal in one of four study periods.	Biological: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Experimental: LY900014 After Meal Individualized dose of LY900014 administered SC 20 minutes after start of meal in one of four study periods.	Biological: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro (Humalog) Before Meal Individualized dose of insulin lispro administered SC immediately before meal in one of four study periods.	Biological: Insulin Lispro; Administered SC; Other Names: LY275585 Humalog
Active Comparator: Insulin Lispro (Humalog) After Meal Individualized dose of insulin lispro administered SC 20 minutes after start of meal in one of four study periods.	Biological: Insulin Lispro; Administered SC; Other Names: LY275585 Humalog

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) [Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, and 420 minutes (7 hours)]

   PK: Insulin Lispro AUC for Each Treatment Arm. LY900014 before and after meal and insulin lispro (Humalog) before and after meal were pooled by treatment to evaluate the overall PK of LY900014 and insulin lispro (Humalog) per protocol .

Secondary Outcome Measures

1. Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Curve [Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose]

   GD: Area Under The Baseline Subtracted Glucose Concentration Curve for Each Treatment Arm

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are male or female participants with Type 1 Diabetes Mellitus (T1DM) for at least 1 year

• Have a body mass index (BMI) of 18.5 kilogram per meter square (kg/m²) to 35.0 kg/m²

• Have a glycated hemoglobin (HbA1c) ≤9.0% at screening

• Are on stable prandial insulin and basal insulin (neutral protamine Hagedorn [NPH] insulin, insulin glargine or insulin detemir) for at least 3 months before screening with a total insulin dose demand of less than or equal to (≤) 1.5 units per kilogram per day (U/kg/day)

Exclusion Criteria:

• Are currently enrolled, or have participated within the last 30 days, in a clinical trial or any other type of medical research

• Have or used to have health problems that, in the opinion of the doctor, could make it unsafe to participate in the study

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

• Any significant changes in insulin regimen and/or unstable blood glucose control within the past 3 months prior to screening as assessed by the investigator.

• Are treated with a CSII (insulin pump)

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.	Mainz		Germany
2	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.	Neuss		Germany

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 - Dec 12, 2017
• Statistical Analysis Plan - May 25, 2018

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03341299
• Other Study ID Numbers: 16641; I8B-MC-ITRV; 2017-001500-30
• First Posted: Nov 14, 2017
• Last Update Posted: May 14, 2020
• Last Verified: Apr 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: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Arm/Group Description	Individualized dose of LY900014 or insulin lispro (Humalog) administered subcutaneously (SC) with 21 hours between doses Period 1: LY900014 administered subcutaneously (SC) immediately before meal Period 2: insulin lispro (Humalog) administered SC 20 minutes after start of meal Period 3:LY900014 administered SC 20 minutes after start of meal Period 4: insulin lispro administered SC immediately before meal	Individualized dose of LY900014 or insulin lispro (Humalog) administered subcutaneously (SC) with 21 hours between doses Period 1:LY900014 administered SC 20 minutes after start of meal Period 2: LY900014 administered subcutaneously (SC) immediately before meal Period 3: insulin lispro (Humalog) administered SC immediately before meal Period 4: insulin lispro (Humalog) administered SC 20 minutes after start of meal	Individualized dose of LY900014 or insulin lispro (Humalog) administered subcutaneously (SC) with 21 hours between doses Period 1: insulin lispro (Humalog) administered SC immediately before meal Period 2:LY900014 administered SC 20 minutes after start of meal Period 3: insulin lispro (Humalog) administered SC 20 minutes after start of meal Period 4: LY900014 administered subcutaneously (SC) immediately before meal	Individualized dose of LY900014 or insulin lispro (Humalog) administered subcutaneously (SC) with 21 hours between doses Period 1: insulin lispro (Humalog) administered SC 20 minutes after start of meal Period 2: insulin lispro (Humalog) administered SC immediately before meal Period 3: LY900014 administered subcutaneously (SC) immediately before meal Period 4:LY900014 administered SC 20 minutes after start of meal
Period Title: Period 1
STARTED	9	9	9	9
COMPLETED	9	9	9	9
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	9	9	9	9
COMPLETED	9	9	8	9
NOT COMPLETED	0	0	1	0
Period Title: Period 1
STARTED	9	9	8	9
COMPLETED	9	9	8	9
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	9	9	8	9
COMPLETED	9	9	8	9
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	9	9	8	9
COMPLETED	9	9	8	9
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	9	9	8	9
COMPLETED	9	9	8	9
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	9	9	8	9
COMPLETED	9	9	8	9
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	All randomized participants who received at least 1 dose of study drug.
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.4 (11.3)
Sex: Female, Male (Count of Participants)
Female	9 25%
Male	27 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	36 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	35 97.2%
More than one race	1 2.8%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Germany	36 100%
Duration of Type 1 Diabetes Mellitis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.41 (13.60)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC)
Description	PK: Insulin Lispro AUC for Each Treatment Arm. LY900014 before and after meal and insulin lispro (Humalog) before and after meal were pooled by treatment to evaluate the overall PK of LY900014 and insulin lispro (Humalog) per protocol .
Time Frame	Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, and 420 minutes (7 hours)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug. LY900014 before and after meal and insulin lispro (Humalog) before and after meal were pooled by treatment to evaluate the overall PK of LY900014 and insulin lispro (Humalog) per protocol .

Arm/Group Title	LY900014	Insulin Lispro (Humalog)
Arm/Group Description	All participants who received individualized dose of LY900014 SC before meal or 20 minutes after start of meal	All participants who received individualized dose of insulin lispro (Humalog) SC before meal or 20 minutes after start of meal
Measure Participants	35	35
Geometric Mean (Geometric Coefficient of Variation) [picomoles times hour per Liter]	970 (57)	968 (56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014, Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7734
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least square means
	Estimated Value	0.991
	Confidence Interval	(2-Sided) 95%; 0.932 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Curve
Description	GD: Area Under The Baseline Subtracted Glucose Concentration Curve for Each Treatment Arm
Time Frame	Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable glucodynamic parameters.

Arm/Group Title	LY900014 Before Meal	LY900014 After Meal	Insulin Lispro (Humalog) Before Meal	Insulin Lispro (Humalog) After Meal
Arm/Group Description	Individualized dose of LY900014 administered subcutaneously (SC) immediately before meal in one of four study periods.	Individualized dose of LY900014 administered SC 20 minutes after start of meal in one of four study periods.	Individualized dose of insulin lispro (Humalog) administered SC immediately before meal in one of four study periods.	Individualized dose of insulin lispro administered SC 20 minutes after start of meal in one of four study periods.
Measure Participants	30	29	32	29
Mean (Standard Deviation) [milligrams times hour per deciLiter]	207 (189)	264 (205)	227 (163)	327 (212)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014, Insulin Lispro (Humalog) Before Meal
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7190
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	difference in LS means
	Estimated Value	-14.50
	Confidence Interval	(2-Sided) 95%; -94.38 to 65.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	4 weeks
Adverse Event Reporting Description	All participants who received at least 1 dose of study drug.
Arm/Group Title	LY900014 Before Meal		LY900014 After Meal		Insulin Lispro (Humalog) Before Meal		Insulin Lispro (Humalog) After Meal
Arm/Group Description	Individualized dose of LY900014 administered subcutaneously (SC) immediately before meal in one of four study periods.		Individualized dose of LY900014 administered SC 20 minutes after start of meal in one of four study periods.		Individualized dose of insulin lispro (Humalog) administered SC immediately before meal in one of four study periods.		Individualized dose of insulin lispro (Humalog) administered SC 20 minutes after start of meal in one of four study periods.
All Cause Mortality
	LY900014 Before Meal		LY900014 After Meal		Insulin Lispro (Humalog) Before Meal		Insulin Lispro (Humalog) After Meal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)		0/36 (0%)		0/35 (0%)
Serious Adverse Events
	LY900014 Before Meal		LY900014 After Meal		Insulin Lispro (Humalog) Before Meal		Insulin Lispro (Humalog) After Meal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)		0/36 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	LY900014 Before Meal		LY900014 After Meal		Insulin Lispro (Humalog) Before Meal		Insulin Lispro (Humalog) After Meal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		3/35 (8.6%)		3/36 (8.3%)		0/35 (0%)
General disorders
Injection Site Reaction	0/35 (0%)	0	3/35 (8.6%)	3	1/36 (2.8%)	1	0/35 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	0/35 (0%)	0	0/35 (0%)	0	2/36 (5.6%)	2	0/35 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.