A Study of LY900014 in Japanese Participants With Type 1 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03407118
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.8
• Patients Per Site Per Month: 6.5

Study Details

Study Description

Brief Summary

This study will compare LY900014, a drug that lowers blood sugar, with insulin lispro (Humalog). Both drugs will be given by injection under the skin of the abdomen. This study will be conducted in participants with type 1 diabetes to investigate how quickly and how much LY900014 is absorbed and the effect of LY900014 on blood sugar levels in comparison with insulin lispro. The study will last about 3 to 6 weeks for each participant, not including screening.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Pharmacokinetics and Glucodynamics of LY900014 Compared to Insulin Lispro (Humalog) Following Single Dose Administration in Japanese Patients With Type 1 Diabetes Mellitus
• Actual Study Start Date: Feb 17, 2018
• Actual Primary Completion Date: Jun 23, 2018
• Actual Study Completion Date: Jul 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 Single, 15 units (U)LY900014 administered subcutaneously (SC) in one of two study periods in Japanese Patients With Type 1 Diabetes Mellitus (T1DM).	Drug: LY900014; Administered SC.; Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro (Humalog) Single, 15 U insulin lispro administered SC in one of two study periods in Japanese Patients With Type 1 Diabetes Mellitus.	Drug: Insulin Lispro; Administered SC.; Other Names: LY275585 Humalog

Outcome Measures

Primary Outcome Measures

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

   PK: Insulin Lispro AUC from 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 Treatment Arm [Predose, every minute from run-in and for the duration of the EC until up to 10 hours postdose]

   Gtot Over Duration of Clamp for Each Treatment Arm. 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 (EC) 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: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are Japanese male or female participant with a diagnosis of T1DM, based on the World Health Organization classification, for at least 1 year prior to screening

• Have a body mass index (BMI) of 18.5 to 30.0 kilograms per square meter (kg/m²)

• Have a glycated hemoglobin <9.0% at screening

Exclusion Criteria:

• Have, except for current regimen of insulin therapy and concomitant medication(s), regular use of or intended use of any over-the-counter or prescription medications or nutritional supplements that treat hyperglycemia or insulin resistance or that promote weight loss within 14 days before dosing

• Are receiving chronic (lasting longer than 14 consecutive days) systemic or inhaled glucocorticoid therapy (excluding topical, intra-articular, and intraocular preparations), or have received such therapy within the 4 weeks before screening

• Have a history of renal impairment (exclusion only if estimated glomerular filtration rate [GFR] <60 milliliters/minute/1.73 square meters [GFR is estimated according to a formula recommended by the Japanese Society of Nephrology]), or have a serum creatinine level ≥126 micromoles per liter (μmol/L) (>1.42 milligrams per deciliter [mg/dL]) (male) or ≥111 μmol/L (>1.25 mg/dL) (female)

• Have a history of deep vein thrombosis of the leg, or repeated episodes of deep leg vein thrombosis in first-degree relatives (parents, siblings, or children), as determined by the investigator

• Have proliferative retinopathy or maculopathy and/or severe neuropathy; in particular, autonomic neuropathy, as determined by the investigator based on a recent (<1.5 years) ophthalmologic examination

• Have had any significant changes in insulin regimen and/or unstable blood glucose control within the past 3 months prior to screening, as determined by the investigator

• Require daily insulin treatment >1.5 units per kilogram (U/kg)

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.	Fukuoka		Japan	812-0025

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 - Nov 7, 2017
• Statistical Analysis Plan - Aug 16, 2018

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03407118
• Other Study ID Numbers: 16645; I8B-MC-ITRZ
• First Posted: Jan 23, 2018
• Last Update Posted: May 1, 2020
• Last Verified: Aug 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	LY900014\Insulin Lispro (Humalog)	Insulin Lispro (Humalog)\LY900014
Arm/Group Description	Period 1: A single dose of 15 Units (U) LY900014 administered subcutaneously (SC) . Period 2: A single dose of 15 U insulin lispro (Humalog) administered SC with up to 28 days between doses	Period 1: A single dose of 15 U insulin lispro (Humalog) administered SC. Period 2: A single dose of 15 Units (U) LY900014 administered subcutaneously (SC) . with up to 28 days between doses.
Period Title: Period 1
STARTED	14	17
Received at Least 1 Dose of Study Drug	14	17
COMPLETED	14	17
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	14	17
Received at Least 1 Dose of Study Drug	13	17
COMPLETED	13	17
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All randomized participants who received at least 1 dose of study drug.
Overall Participants	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.5 (11.3)
Sex: Female, Male (Count of Participants)
Female	18 58.1%
Male	13 41.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	31 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	31 100%
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)
Japan	31 100%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	59.62 (8.29)
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	161.35 (7.44)
Body Mass Index (kilograms per meter squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter squared]	22.85 (2.44)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	15 U LY900014	15 U Insulin Lispro (Humalog)
Arm/Group Description	A single dose of 15 Units (U) LY900014 administered subcutaneously (SC) in one of two study periods.	A single dose of 15 U insulin lispro (Humalog) administered SC in one of two study periods.
Measure Participants	31	30
Geometric Mean (Geometric Coefficient of Variation) [picomols times hour per Liter]	1930 (59)	1980 (20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	15 U LY900014, 15 U Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of least square means
	Estimated Value	0.967
	Confidence Interval	(2-Sided) 95%; 0.803 to 1.17
	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 Treatment Arm
Description	Gtot Over Duration of Clamp for Each Treatment Arm. 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 (EC) 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	Predose, every minute from run-in and for the duration of the EC until up to 10 hours postdose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	15 U LY900014	15 U Insulin Lispro (Humalog)
Arm/Group Description	A single dose of 15 Units (U) LY900014 administered subcutaneously (SC) in one of two study periods.	A single dose of 15 U insulin lispro (Humalog) administered SC in one of two study periods.
Measure Participants	31	30
Geometric Mean (Geometric Coefficient of Variation) [milligrams per kilogram]	1190 (54)	1250 (34)

Adverse Events

Time Frame	Baseline up to 56 weeks
Adverse Event Reporting Description	All randomized participants.
Arm/Group Title	LY900014		Insulin Lispro (Humalog)
Arm/Group Description	A single dose of 15 Units (U) LY900014 administered subcutaneously (SC) . in one of two study periods.		A single dose of 15 U insulin lispro (Humalog) administered SC in one of two study periods.
All Cause Mortality
	LY900014		Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/30 (0%)
Serious Adverse Events
	LY900014		Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	LY900014		Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/31 (19.4%)		7/30 (23.3%)
Gastrointestinal disorders
nausea	3/31 (9.7%)	3	1/30 (3.3%)	1
vomiting	2/31 (6.5%)	2	2/30 (6.7%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/31 (3.2%)	1	2/30 (6.7%)	2
Nervous system disorders
Headache	3/31 (9.7%)	4	4/30 (13.3%)	4

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.