A Study of LY900014 in Participants With Type 1 Diabetes on Insulin Injection Therapy

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02703350
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 4
• Duration (Months): 4
• Patients Per Site Per Month: 7.5

Study Details

Study Description

Brief Summary

The study will be conducted in participants with type1 diabetes on insulin injection therapy to investigate how the body processes LY900014 and the effect of LY900014 on blood sugar levels. Side effects and tolerability will be documented. The study will be conducted in two parts (Part A and Part B) to achieve its objectives. Participants are expected to enroll in both parts.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Pharmacokinetics, Glucodynamics, Safety, and Tolerability of LY900014 in Patients With Type 1 Diabetes Mellitus on Multiple Daily Insulin Injection Therapy
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 - Test (Part A) Individualized doses of LY900014 administered by injection under the skin once in each of 3 periods	Drug: LY900014; Administered subcutaneously (SC); Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro - Reference (Part A) Individualized doses of insulin lispro reference formulation administered by injection under the skin once in each of 3 periods	Drug: Insulin Lispro; Administered SC; Other Names: LY275585
Experimental: LY900014 - Test (Part B) Individualized doses of LY900014 administered by injection under the skin immediately before each meal for 14 days	Drug: LY900014; Administered subcutaneously (SC); Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro - Reference (Part B) Individualized doses of insulin lispro reference formulation administered by injection under the skin immediately before each meal for 14 days	Drug: Insulin Lispro; Administered SC; Other Names: LY275585

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part A) [Day 1: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment]

   PK: Insulin Lispro AUC(0-5h) (Part A)

2. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B) [Days 1 and 14: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment]

   PK: Insulin Lispro AUC(0-5h) (Part B)

Secondary Outcome Measures

1. Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part A) [Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes]

   PD: AUC(0-5h) of Glucose Relative to a MMTT (Part A)

2. Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B) [Days 1 and 14: Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes in each study period]

   PD: AUC(0-5h) of Glucose Relative to a MMTT (Part B)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are male or female participants with Type 1 Diabetes Mellitus (T1DM) on a stable multiple daily injection regimen with a short-acting as well as a long-acting insulin

• Have a body mass index (BMI) ranging from 18.5 to 33.0 kilogram per square meter (kg/m²), inclusive, at screening

• Have blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results acceptable for the study

• Have had no episodes of severe hypoglycemia in the past 6 months (requiring assistance in treatment by a second party)

• Have venous access sufficient to allow for blood sampling

• Have provided written consent and are willing to follow study procedures and commit to the study duration

Exclusion Criteria:

• Are currently enrolled, or have participated within the last 30 days, in a clinical trial or any other type of medical research judged to be incompatible with this study

• Have previously completed or withdrawn from this study

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

• Had blood loss of more than 500 milliliters (mL) within the last month

• Are treated with a continuous subcutaneous insulin infusion (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

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)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02703350
• Other Study ID Numbers: 16068; I8B-FW-ITRG; 2015-004737-27
• First Posted: Mar 9, 2016
• Last Update Posted: Jun 17, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Lispro

Study Results

Participant Flow

Pre-assignment Detail	Two-part study compared individualized doses of LY900014 (Test) to insulin lispro (Reference). Part A: LY900014 or insulin lispro once subcutaneously (SC) before, at, or after start of meal in each of 6 periods. Minimum 1 day washout. Part B: LY900014 or insulin lispro SC before meals for 14 days. Participants were expected to complete both parts.

Arm/Group Title	Part A Sequence 1, ABFCED	Part A Sequence 2, BCADFE	Part A Sequence 3, CDBEAF	Part A Sequence 4, DECFBA	Part A Sequence 5, EFDACB	Part A Sequence 6, FAEBDC	Part B LY900014 (Test)	Part B Insulin Lispro (Reference)
Arm/Group Description	A = LY900014 Test (15 minutes [mins] before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).	A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).	A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).	A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).	A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).	A = LY900014 Test (15 mins before meal). B = LY900014 Test (at mealtime). C = LY900014 Test (15 mins after start of meal). D = Insulin Lispro Reference (15 mins before meal). E = Insulin Lispro Reference (at mealtime). F = Insulin Lispro Reference (15 mins after start of meal).	Individualized doses of LY900014 Test administered SC immediately before meals for 14 days.	Individualized doses of Insulin Lispro Reference administered SC immediately before meals for 14 days.
Period Title: Period One (Part A)
STARTED	5	5	5	5	5	5	0	0
Received Study Drug	5	5	5	5	5	5	0	0
COMPLETED	5	5	5	5	5	5	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Period One (Part A)
STARTED	5	5	5	5	5	5	0	0
Received Study Drug	5	5	5	5	5	5	0	0
COMPLETED	5	5	5	5	5	5	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Period One (Part A)
STARTED	5	5	5	5	5	5	0	0
Received Study Drug	5	5	5	5	5	5	0	0
COMPLETED	5	5	5	5	5	5	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Period One (Part A)
STARTED	5	5	5	5	5	5	0	0
Received Study Drug	5	5	5	5	5	5	0	0
COMPLETED	5	5	5	5	5	5	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Period One (Part A)
STARTED	5	5	5	5	5	5	0	0
Received Study Drug	5	5	5	5	5	5	0	0
COMPLETED	5	5	5	5	5	5	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Period One (Part A)
STARTED	5	5	5	5	5	5	0	0
Received Study Drug	5	5	5	5	5	5	0	0
COMPLETED	5	5	5	5	5	5	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Period One (Part A)
STARTED	0	0	0	0	0	0	15	15
Received Study Drug	0	0	0	0	0	0	15	15
COMPLETED	0	0	0	0	0	0	15	15
NOT COMPLETED	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Individualized doses of LY900014 (Test) or insulin lispro (Reference) administered once SC at various mealtime intervals in each of six periods (Part A) and immediately before meals for 14 days (Part B).
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.2 (12.8)
Sex: Female, Male (Count of Participants)
Female	6 20%
Male	24 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	30 100%
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	30 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Germany	30 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part A)
Description	PK: Insulin Lispro AUC(0-5h) (Part A)
Time Frame	Day 1: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment

Outcome Measure Data

Analysis Population Description

All participants in Part A who received study drug and had evaluable PK data. For one participant in the LY900014 - Test (Part A) group, the insulin lispro PK profile (period three) was excluded from the mean PK analysis, as there was no absorption phase observed.

Arm/Group Title	Insulin Lispro - Reference (Part A)	LY900014 - Test (Part A)
Arm/Group Description	Individualized doses of insulin lispro (Reference) administered once SC in three of six periods.	Individualized doses of LY900014 (Test) administered once SC in three of six periods.
Measure Participants	30	30
Geometric Mean (Geometric Coefficient of Variation) [picomole*hour per liter (pmol*h/L)]	719 (52)	783 (51)

2. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B)
Description	PK: Insulin Lispro AUC(0-5h) (Part B)
Time Frame	Days 1 and 14: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment

Outcome Measure Data

Analysis Population Description

All participants in Part B who received study drug and had evaluable PK data.

Arm/Group Title	Insulin Lispro - Reference (Part B)	LY900014 - Test (Part B)
Arm/Group Description	Individualized doses of insulin lispro (Reference) administered SC immediately before each meal for 14 days.	Individualized doses of LY900014 (Test) administered SC immediately before each meal for 14 days.
Measure Participants	15	15
Day 1	751 (40)	780 (63)
Day 14	718 (50)	771 (61)

3. Secondary Outcome

Title	Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part A)
Description	PD: AUC(0-5h) of Glucose Relative to a MMTT (Part A)
Time Frame	Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes

Outcome Measure Data

Analysis Population Description

All participants in Part A who received study drug immediately before a meal (0 min) and had evaluable PD data. Data were excluded if the participant did not keep identical insulin lispro dose during the MMTT assessments, did not complete the entire test meal, or had significant changes in nutrient consumption of the test meal.

Arm/Group Title	Insulin Lispro - Reference 0 Min (Part A)	LY900014 - Test 0 Min (Part A)
Arm/Group Description	Individualized doses of insulin lispro (Reference) administered once SC immediately before meal in one of six periods.	Individualized doses of LY900014 (Test) administered once SC immediately before meal in one of six periods.
Measure Participants	29	27
Mean (Standard Deviation) [milligram*hour/deciliter (mg*h/dL)]	495 (161)	537 (184)

4. Secondary Outcome

Title	Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B)
Description	PD: AUC(0-5h) of Glucose Relative to a MMTT (Part B)
Time Frame	Days 1 and 14: Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes in each study period

Outcome Measure Data

Analysis Population Description

All participants in Part B who received study drug and had evaluable PD data. Data were excluded if the participant did not keep identical insulin lispro dose during the MMTT assessments, did not complete the entire test meal, or had significant changes in nutrient consumption of the test meal.

Arm/Group Title	Insulin Lispro - Reference (Part B)	LY900014 - Test (Part B)
Arm/Group Description	Individualized doses of insulin lispro (Reference) administered SC immediately before each meal for 14 days.	Individualized doses of LY900014 (Test) administered SC immediately before each meal for 14 days.
Measure Participants	15	14
Day 1	533 (205)	404 (131)
Day 14	547 (239)	411 (130)

Adverse Events

Arm/Group Title	Insulin Lispro - Reference -15 Min (Part A)		Insulin Lispro - Reference 0 Min (Part A)		Insulin Lispro - Reference +15 Min (Part A)		LY900014 - Test -15 Min (Part A)		LY900014 - Test 0 Min (Part A)		LY900014 - Test +15 Min (Part A)		Insulin Lispro Open Label - (Part A)		Insulin Lispro - Reference (Part B)		LY900014 - Test (Part B)		Insulin Lispro Open Label - (Part B)
Arm/Group Description	Individualized doses of insulin lispro (Reference) administered once SC 15 minutes prior to meal in one of six periods.		Individualized doses of insulin lispro (Reference) administered once SC immediately before meal in one of six periods.		Individualized doses of insulin lispro (Reference) administered once SC 15 minutes after start of meal in one of six periods.		Individualized doses of LY900014 (Test) administered once SC 15 minutes prior to meal in one of six periods.		Individualized doses of LY900014 (Test) administered once SC immediately before meal in one of six periods.		Individualized doses of LY900014 (Test) administered once SC 15 minutes after start of meal in one of six periods.		Individualized doses of insulin lispro administered SC between periods.		Individualized doses of insulin lispro (Reference) administered SC immediately before meals for 14 days.		Individualized doses of LY900014 (Test) administered SC immediately before meals for 14 days.		Individualized doses of insulin lispro administered SC immediately before meals.
All Cause Mortality
	Insulin Lispro - Reference -15 Min (Part A)		Insulin Lispro - Reference 0 Min (Part A)		Insulin Lispro - Reference +15 Min (Part A)		LY900014 - Test -15 Min (Part A)		LY900014 - Test 0 Min (Part A)		LY900014 - Test +15 Min (Part A)		Insulin Lispro Open Label - (Part A)		Insulin Lispro - Reference (Part B)		LY900014 - Test (Part B)		Insulin Lispro Open Label - (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Lispro - Reference -15 Min (Part A)		Insulin Lispro - Reference 0 Min (Part A)		Insulin Lispro - Reference +15 Min (Part A)		LY900014 - Test -15 Min (Part A)		LY900014 - Test 0 Min (Part A)		LY900014 - Test +15 Min (Part A)		Insulin Lispro Open Label - (Part A)		Insulin Lispro - Reference (Part B)		LY900014 - Test (Part B)		Insulin Lispro Open Label - (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	0/30 (0%)		0/30 (0%)		0/30 (0%)		0/30 (0%)		0/30 (0%)		0/30 (0%)		0/30 (0%)		0/15 (0%)		0/15 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Insulin Lispro - Reference -15 Min (Part A)		Insulin Lispro - Reference 0 Min (Part A)		Insulin Lispro - Reference +15 Min (Part A)		LY900014 - Test -15 Min (Part A)		LY900014 - Test 0 Min (Part A)		LY900014 - Test +15 Min (Part A)		Insulin Lispro Open Label - (Part A)		Insulin Lispro - Reference (Part B)		LY900014 - Test (Part B)		Insulin Lispro Open Label - (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	0/30 (0%)		1/30 (3.3%)		0/30 (0%)		0/30 (0%)		0/30 (0%)		1/30 (3.3%)		0/30 (0%)		2/15 (13.3%)		1/15 (6.7%)		0/30 (0%)
General disorders
Asthenia	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/30 (0%)	0
Pyrexia	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/30 (0%)	0
Infections and infestations
Sinusitis	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/30 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/30 (0%)	0
Nervous system disorders
Headache	0/30 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	2/15 (13.3%)	2	0/15 (0%)	0	0/30 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dry throat	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/30 (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.