A Comparative Study of LY900014 to Insulin Lispro (Humalog) in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03286751
• Collaborator: (none)
• Enrollment: 42
• Locations: 2
• Arms: 2
• Actual Duration (Months): 3.8
• Patients Per Site: 21
• Patients Per Site Per Month: 5.5

Study Details

Study Description

Brief Summary

This study compares LY900014, a drug that lowers blood sugar, with insulin lispro (Humalog). Both drugs are given by injection under the skin of the abdomen. The study will be conducted in healthy people to investigate how quickly and how much LY900014 is absorbed and the effect of different doses of LY900014 on blood sugar levels in comparison with insulin lispro. The study will last about 7 to 12 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; Drug: Insulin Lispro	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 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 and Humalog Across Different Subcutaneous Doses in Healthy Subjects
• Actual Study Start Date: Oct 13, 2017
• Actual Primary Completion Date: Feb 6, 2018
• Actual Study Completion Date: Feb 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 Single dose of 7 units (U), 15 U, and 30 U of LY900014 administered subcutaneously (SC) in three of six periods.	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro (Humalog) Single dose of 7 U, 15 U, and 30 U of insulin lispro administered SC in three of six periods.	Drug: Insulin Lispro; Administered SC; Other Names: LY275585 Humalog

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) [Day 1: Pre-dose, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose]

   Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours Post Dose [AUC(0-10h)]

Secondary Outcome Measures

1. Glucodynamics: Total Amount of Glucose Infused (Gtot) [Day 1: Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose]

   Glucodynamics: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 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 one month after 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

• 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

• Have previously participated or withdrawn from this study

• Have donated blood or have blood loss of more than 500 mL within the past 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.	Mainz		Germany	55116
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	41460

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 - Jun 26, 2017
• Statistical Analysis Plan - Apr 18, 2018

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03286751
• Other Study ID Numbers: 16898; 2017-001859-32; I8B-MC-ITSH
• First Posted: Sep 18, 2017
• Last Update Posted: May 1, 2020
• Last Verified: Feb 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, Type 2; Insulin Lispro

Study Results

Participant Flow

Pre-assignment Detail	This was a 6-period crossover study in which participants received a single 7 Unit (U), 15 U, or 30 U subcutaneous (SC) dose of LY900014 or Humalog in one of six sequences. There was a washout period of ≥ 3 days between each euglycemic clamp procedure.

Arm/Group Title	Sequence 1: ABFCED	Sequence 2: BCADFE	Sequence 3: CDBEAF	Sequence 4: DECFBA	Sequence 5: EFDACB	Sequence 6: FAEBDC
Arm/Group Description	Participants received a single SC dose in each treatment period. A = 7 U LY900014 B = 15 U LY900014 F = 30 U Humalog C = 30 U LY900014 E = 15 U Humalog D = 7 U Humalog	Participants received a single SC dose in each treatment period. B = 15 U LY900014 C = 30 U LY900014 A = 7 U LY900014 D = 7 U Humalog F = 30 U Humalog E = 15 U Humalog	Participants received a single SC dose in each treatment period. C = 30 U LY900014 D = 7 U Humalog B = 15 U LY900014 E = 15 U Humalog A = 7 U LY900014 F = 30 U Humalog	Participants received a single SC dose in each treatment period. D = 7 U Humalog E = 15 U Humalog C = 30 U LY900014 F = 30 U Humalog B = 15 U LY900014 A = 7 U LY900014	Participants received a single SC dose in each treatment period. E = 15 U Humalog F = 30 U Humalog D = 7 U Humalog A = 7 U LY900014 C = 30 U LY900014 B = 15 U LY900014	Participants received a single SC dose in each treatment period. F = 30 U Humalog A = 7 U LY900014 E = 15 U Humalog B = 15 U LY900014 D = 7 U Humalog C = 30 U LY900014
Period Title: Period 1
STARTED	7	7	7	7	7	7
Received at Least One Dose of Study Drug	7	7	7	7	7	7
COMPLETED	7	7	7	7	7	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	7	7	7	7	7
COMPLETED	7	7	7	7	6	7
NOT COMPLETED	0	0	0	0	1	0
Period Title: Period 1
STARTED	7	7	7	7	6	7
COMPLETED	7	7	7	7	6	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	7	7	7	6	7
COMPLETED	7	6	7	7	6	7
NOT COMPLETED	0	1	0	0	0	0
Period Title: Period 1
STARTED	7	6	7	7	6	7
COMPLETED	7	6	7	7	6	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	6	7	7	6	7
COMPLETED	7	6	7	7	6	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	6	7	7	6	7
COMPLETED	7	6	7	7	6	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	6	7	7	6	7
COMPLETED	7	6	7	7	6	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	6	7	7	6	7
COMPLETED	7	6	7	7	6	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	6	7	7	6	7
COMPLETED	7	6	7	7	5	7
NOT COMPLETED	0	0	0	0	1	0
Period Title: Period 1
STARTED	7	6	7	7	5	7
COMPLETED	7	6	7	7	5	7
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	All participants who received at least on dose of study drug.
Overall Participants	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.9 (11.6)
Sex: Female, Male (Count of Participants)
Female	15 35.7%
Male	27 64.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.8%
Not Hispanic or Latino	40 95.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 4.8%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	40 95.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Germany	42 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC)
Description	Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours Post Dose [AUC(0-10h)]
Time Frame	Day 1: Pre-dose, 5, 10, 15, 20, 25, 30, 35, 40, 50, 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 received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	7 U Humalog	7 U LY900014	15 U Humalog	15 U LY900014	30 U Humalog	30 U LY900014
Arm/Group Description	Single SC dose 7 U Humalog.	Single SC dose 7 U LY900014.	Single SC dose 15 U Humalog.	Single SC dose 15 U LY900014.	Single SC dose 30 U Humalog.	Single SC dose 30 U LY900014.
Measure Participants	40	40	41	40	40	41
Geometric Mean (Geometric Coefficient of Variation) [picomole * hour per liter(pmol*/L)]	649 (16)	656 (17)	1400 (19)	1450 (17)	3050 (18)	3180 (20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	7 U Humalog, 7 U LY900014
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5495
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.974 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	15 U Humalog, 15 U LY900014
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2236
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.986 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	30 U Humalog, 30 U LY900014
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0727
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.997 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Glucodynamics: Total Amount of Glucose Infused (Gtot)
Description	Glucodynamics: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp
Time Frame	Day 1: Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and completed at least one clamp procedure.

Arm/Group Title	7 U Humalog	7 U LY900014	15 U Humalog	15 U LY900014	30 U Humalog	30 U LY900014
Arm/Group Description	Single SC dose 7 U Humalog.	Single SC dose 7 U LY900014.	Single SC dose 15 U Humalog.	Single SC dose 15 U LY900014.	Single SC dose 30 U Humalog.	Single SC dose 30 U LY900014.
Measure Participants	40	40	41	40	40	41
Geometric Mean (Geometric Coefficient of Variation) [milligrams per kilogram (mg/kg)]	1120 (53)	1080 (60)	1970 (44)	1860 (45)	3290 (32)	3030 (36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	7 U Humalog, 7 U LY900014
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5749
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	15 U Humalog, 15 U LY900014
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1578
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	30 U Humalog, 30 U LY900014
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1351
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Baseline to study completion (up to 12 weeks)
Arm/Group Title	7 U LY900014		15 U LY900014		30 U LY900014		7 U Humalog		15 U Humalog		30 U Humalog
Arm/Group Description	Single SC dose 7 U LY900014.		Single SC dose 15 U LY900014.		Single SC dose 30 U LY900014.		Single SC dose 7 U Humalog.		Single SC dose 15 U Humalog.		Single SC dose 15 U Humalog.
All Cause Mortality
	7 U LY900014		15 U LY900014		30 U LY900014		7 U Humalog		15 U Humalog		30 U Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)		0/41 (0%)		0/40 (0%)		0/41 (0%)		0/40 (0%)
Serious Adverse Events
	7 U LY900014		15 U LY900014		30 U LY900014		7 U Humalog		15 U Humalog		30 U Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)		0/41 (0%)		0/40 (0%)		0/41 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	7 U LY900014		15 U LY900014		30 U LY900014		7 U Humalog		15 U Humalog		30 U Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/40 (17.5%)		5/40 (12.5%)		14/41 (34.1%)		8/40 (20%)		6/41 (14.6%)		5/40 (12.5%)
Gastrointestinal disorders
Nausea	1/40 (2.5%)	1	2/40 (5%)	2	3/41 (7.3%)	3	1/40 (2.5%)	1	1/41 (2.4%)	1	2/40 (5%)	2
General disorders
Injection site reaction	1/40 (2.5%)	1	1/40 (2.5%)	1	6/41 (14.6%)	6	0/40 (0%)	0	2/41 (4.9%)	2	0/40 (0%)	0
Nervous system disorders
Headache	6/40 (15%)	6	4/40 (10%)	4	6/41 (14.6%)	6	8/40 (20%)	8	3/41 (7.3%)	3	3/40 (7.5%)	3

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.