A Study of LY900014 Versus Insulin Lispro (Humalog) on High Blood Sugar in Participants With Type 1 Diabetes Who Use Insulin Pumps

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04276207
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 5.5
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

The main purpose of this study is to compare LY900014 to insulin lispro (Humalog) in participants with type 1 diabetes who are using an insulin pump and have high blood sugar after eating. For each participant, the study will last about two to nine weeks.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Effects of LY900014 on Recovery From Hyperglycemia Compared to Humalog in Subjects With Type 1 Diabetes Mellitus (T1DM) on Continuous Subcutaneous Insulin Infusion
• Actual Study Start Date: Feb 25, 2020
• Actual Primary Completion Date: Aug 10, 2020
• Actual Study Completion Date: Aug 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 100 U/mL LY900014 100 units per milliliter (U/mL) LY900014 administered by continuous subcutaneous insulin infusion (CSII) in one of two study periods.	Drug: LY900014; Administered by CSII
Active Comparator: 100 U/mL Insulin Lispro (Humalog) 100 U/mL Insulin Lispro (Humalog) administered by CSII in one of two study periods.	Drug: Insulin Lispro; Administered by CSII; Other Names: Humalog LY275585

Outcome Measures

Primary Outcome Measures

1. Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Missed Meal Bolus [Day 1: Baseline up to 5 hours after missed meal bolus]

   Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 Milligrams per deciliter (mg/dL).

2. Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Pump Suspension [Day 2: Baseline up to 5 hours after pump suspension]

   Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 mg/dL.

Secondary Outcome Measures

1. Pharmacodynamics (PD): Maximum Observed Plasma Glucose (PGmax) Following Administration of LY900014 and Insulin Lispro (Humalog) [Day 1: Baseline up to 5 hours after missed meal bolus and Day 2: Baseline up to 5 hours after pump suspension]

   PD: PGmax following administration of LY900014 and insulin lispro (Humalog)

2. Pharmacokinetics (PK): Time to Maximum Observed Insulin Lispro Concentration (Tmax) Following Administration of LY900014 and Insulin Lispro (Humalog) [Day 1: Baseline up to 5 hours after missed meal bolus and Day 2: Baseline up to 5 hours after pump suspension]

   PK: Tmax following administration of LY900014 and insulin lispro (Humalog)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female participants with type 1 diabetes

• Body mass index (BMI) between 18.5 and 30.0 kilograms per square meter, inclusive

• Hemoglobin A1c (HbA1c) less than or equal to 8.5 percent (%)

• Using CSII and stable insulin regimen for at least 3 months prior to inclusion into the trial

Exclusion Criteria:

• Known or suspected hypersensitivity to investigational medical product(s) or related products

• Receipt of any medicinal product in clinical development within 30 days or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before randomization in this trial

• Known slowing of gastric emptying and or gastrointestinal surgery that, in the opinion of the investigator, might change gastrointestinal motility and food absorption

• Proliferative retinopathy or maculopathy as judged by the Investigator based on a recent (less than 1.5 years) ophthalmologic examination

• Widespread subcutaneous lipodystrophy in the abdomen

• Current use of any glucose-lowering agents other than insulin within 3 months prior to screening

• Chronic or recent use of corticosteroids

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Profil Mainz GmbH & Co. KG	Mainz	Rheinland-Pfalz	Germany	55116

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 - Jan 22, 2020
• Statistical Analysis Plan - Jul 15, 2020

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04276207
• Other Study ID Numbers: 17277; I8B-MC-ITST; 2019-003493-13
• First Posted: Feb 19, 2020
• Last Update Posted: Aug 25, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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	Sequence AB (LY900014, Insulin Lispro (Humalog))	Sequence BA (Insulin Lispro (Humalog), LY900014))
Arm/Group Description	Period 1: Participants received 100 units per milliliter (U/mL) of LY900014 administered by continuous subcutaneous insulin infusion (CSII). Period 2: Participants received 100 U/mL of Insulin lispro Humalog) administered by CSII.	Period 1: Participants received 100 U/mL of Insulin lispro (Humalog) administered by CSII. Period 2: Participants received 100 U/mL of LY900014 administered by CSII.
Period Title: Period 1
STARTED	15	17
Received at Least One Dose of Study Drug	15	17
COMPLETED	15	16
NOT COMPLETED	0	1
Period Title: Period 1
STARTED	15	16
COMPLETED	15	16
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	15	16
COMPLETED	15	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	100 U/mL LY900014 and 100 U/mL Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL LY900014 administered by CSII in one of two study periods. Participants received 100 U/mL Insulin Lispro (Humalog) administered by CSII in one of two study periods.
Overall Participants	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.8 (9.57)
Sex: Female, Male (Count of Participants)
Female	9 28.1%
Male	23 71.9%
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	32 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Germany	32 100%

Outcome Measures

1. Primary Outcome

Title	Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Missed Meal Bolus
Description	Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 Milligrams per deciliter (mg/dL).
Time Frame	Day 1: Baseline up to 5 hours after missed meal bolus

Outcome Measure Data

Analysis Population Description

All participants who received both study treatments with the same insulin dose and achieved recovery from hyperglycemia on day 1

Arm/Group Title	100 U/mL LY900014	100 U/mL Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 administered by CSII in one of the two study periods.	Participants received 100 U/mL of Insulin lispro (Humalog) administered by CSII in one of the two study periods.
Measure Participants	21	21
Median (Full Range) [Hours]	1.79	2.55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	100 U/mL LY900014, 100 U/mL Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1450
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.377
	Confidence Interval	(2-Sided) 95%; -0.896 to 0.142
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Pump Suspension
Description	Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 mg/dL.
Time Frame	Day 2: Baseline up to 5 hours after pump suspension

Outcome Measure Data

Analysis Population Description

All participants who received both study treatments with the same insulin dose and achieved recovery from hyperglycemia on day 2

Arm/Group Title	100 U/mL LY900014	100 U/mL Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 administered by CSII in one of the two study periods.	Participants received 100 U/mL of Insulin lispro (Humalog) administered by CSII in one of the two study periods.
Measure Participants	28	28
Median (Full Range) [Hours]	1.53	1.78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	100 U/mL LY900014, 100 U/mL Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.262
	Confidence Interval	(2-Sided) 95%; -0.406 to -0.117
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Pharmacodynamics (PD): Maximum Observed Plasma Glucose (PGmax) Following Administration of LY900014 and Insulin Lispro (Humalog)
Description	PD: PGmax following administration of LY900014 and insulin lispro (Humalog)
Time Frame	Day 1: Baseline up to 5 hours after missed meal bolus and Day 2: Baseline up to 5 hours after pump suspension

Outcome Measure Data

Analysis Population Description

All participants who received both study treatments with the same insulin dose and achieved recovery from hyperglycemia on days 1 and 2

Arm/Group Title	100 U/mL LY900014	100 U/mL Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 administered by CSII in one of the two study periods.	Participants received 100 U/mL of Insulin lispro (Humalog) administered by CSII in one of the two study periods.
Measure Participants	28	28
Day 1	297 (27.6)	309 (24.9)
Day 2	259 (11.1)	265 (9.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	100 U/mL LY900014, 100 U/mL Insulin Lispro (Humalog)
	Comments	Day 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0173
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.61
	Confidence Interval	(2-Sided) 95%; -22.73 to -2.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	100 U/mL LY900014, 100 U/mL Insulin Lispro (Humalog)
	Comments	Day 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0243
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.75
	Confidence Interval	(2-Sided) 95%; -10.69 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Pharmacokinetics (PK): Time to Maximum Observed Insulin Lispro Concentration (Tmax) Following Administration of LY900014 and Insulin Lispro (Humalog)
Description	PK: Tmax following administration of LY900014 and insulin lispro (Humalog)
Time Frame	Day 1: Baseline up to 5 hours after missed meal bolus and Day 2: Baseline up to 5 hours after pump suspension

Outcome Measure Data

Analysis Population Description

All participants who received both study treatments with the same insulin dose and achieved recovery from hyperglycemia on days 1 and 2

Arm/Group Title	100 U/mL LY900014	100 U/mL Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 administered by CSII in one of the two study periods.	Participants received 100 U/mL of Insulin lispro (Humalog) administered by CSII in one of the two study periods.
Measure Participants	28	28
Day 1	0.75	0.83
Day 2	0.92	0.92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	100 U/mL LY900014, 100 U/mL Insulin Lispro (Humalog)
	Comments	Day 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.945
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	100 U/mL LY900014, 100 U/mL Insulin Lispro (Humalog)
	Comments	Day 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.888
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Baseline Up To 42 Days
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	100 U/mL LY900014		100 U/mL Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 administered by CSII in one of the two study periods.		Participants received 100 U/mL of Insulin lispro (Humalog) administered by CSII in one of the two study periods.
All Cause Mortality
	100 U/mL LY900014		100 U/mL Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)
Serious Adverse Events
	100 U/mL LY900014		100 U/mL Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	100 U/mL LY900014		100 U/mL Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/31 (9.7%)		2/32 (6.3%)
Endocrine disorders
Hyperglycaemia	2/31 (6.5%)	2	0/32 (0%)	0
Nervous system disorders
Headache	2/31 (6.5%)	2	2/32 (6.3%)	2

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.