A Study of LY900014 Administered in Participants With Type 1 Diabetes Using an Insulin Pump

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03056456
• Collaborator: (none)
• Enrollment: 24
• Locations: 2
• Arms: 2
• Actual Duration (Months): 3.8
• Patients Per Site: 12
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

This study will be conducted in participants with type 1 diabetes mellitus to investigate how the human body processes LY900014, a new blood sugar lowering insulin, and its effect on blood sugar levels when it is delivered via an insulin pump. Side effects and tolerability will be documented. The study will last about 4 to 11 weeks for each participant.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Study to Assess the Pharmacokinetics, Glucodynamics, Safety, and Tolerability of LY900014 in Patients With Type 1 Diabetes Mellitus on Continuous Subcutaneous Insulin Infusion Therapy
• Actual Study Start Date: Feb 23, 2017
• Actual Primary Completion Date: Jun 19, 2017
• Actual Study Completion Date: Jun 19, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 LY900014 (Treatment B) delivered via an insulin pump as a continuous infusion under the skin, with various intermittent bolus doses immediately before meals over 3-days per period.	Drug: LY900014; Administered subcutaneously (SC); Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro (Humalog) Insulin lispro (Treatment A) delivered via an insulin pump as a continuous infusion under the skin, with various intermittent bolus doses immediately before meals over 3-days per period.	Drug: Insulin Lispro (Humalog); Administered SC; Other Names: LY275585 Humalog

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours(h) (AUC [0-5 h]) Following Administration of Each Study Arm With a Standard Single-wave Bolus [Days 1 and 3: -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes post dose]

   PK: Insulin Lispro AUC(0-5h)

2. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Following Administration of Each Study Arm With a Standard Dual-wave Bolus [Days 1 and 3: -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes post dose]

   PK: Insulin Lispro AUC(0-5h)

Secondary Outcome Measures

1. Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5h]) of Glucose Relative to Mixed Meal Tolerance Test Following Administration of Each Study Arm With a Standard Single-wave Bolus [Days 1 and 3: -30, -15, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180,195, 210, 225, 240, and 300 minutes post dose]

   GD: Change from baseline in AUC (0-5h) of glucose relative to mixed meal tolerance test (MMTT).

2. Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Glucose Relative to MMTT Following Administration of Each Study Arm With a Standard Dual-wave Bolus [Day 1 and 3: -30, -15, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180,195, 210, 225, 240, and 300 minutes post dose]

   GD: Change from baseline in AUC (0-5h) of glucose relative to MMTT.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female participants with Type 1 Diabetes Mellitus (T1DM) who are receiving insulin therapy via an approved insulin pump

• Have a screening body mass index (BMI) of greater than 18.5 to 33.0 kilograms per meter squared (kg/m²), inclusive

• Have medical and laboratory test results that are acceptable for the study

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

• 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 participating or recently participated in a clinical trial or any other type of medical research judged to be incompatible with this study

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

• Have known allergies to LY900014, insulin lispro, related compounds or any components in the study drug formulations

• Have previously participated or withdrawn from this study

• Have or used to have health problems or medical test results that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Neuss		Germany	41460
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 - Feb 6, 2017
• Statistical Analysis Plan - Feb 24, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03056456
• Other Study ID Numbers: 16727; I8B-MC-ITSC; 2016-004093-18
• First Posted: Feb 17, 2017
• Last Update Posted: May 1, 2020
• Last Verified: Jun 1, 2017

• 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

Recruitment Details	For the time between consecutive periods, participants continued their CSII with their personal pump using Insulin lispro (Humalog) until the evening of Day -1 (after administration of the standardized dinner) of the next period when they will receive either LY900014 or Insulin lispro (Humalog), according to assigned treatment.
Pre-assignment Detail	Participants were randomized to receive LY900014 and Insulin lispro (Humalog) via CSII with intermittent bolus doses, standard single-wave (SS) and standard dual-wave (SD) immediately before meals, over 3 days per period.

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4
Arm/Group Description	Administration modes for LY900014 or Insulin lispro (Humalog) for Days 1 through 3 for breakfast (B): Period 1: Insulin lispro (Humalog) Day 1: B: SD Day 3: B: SD Period 2: Insulin lispro (Humalog) Day 1: B: SS Day 3: B: SS Period 3: LY900014 Day 1: B: SD Day 3: B: SD Period 4: LY900014 Day 1: B: SS Day 3: B: SS	Administration modes for LY900014 or Insulin lispro (Humalog) for Days 1 through 3 for breakfast: Period 1:Insulin lispro (Humalog) Day 1: B: SS Day 3: B: SS Period 2: LY900014 Day 1: B: SS Day 3: B: SS Period 3: Insulin lispro (Humalog) Day 1: B: SD Day 3: B: SD Period 4: LY900014 Day 1: B: SD Day 3: B: SD	Administration modes for LY900014 or Insulin lispro (Humalog) for Days 1 through 3 for breakfast: Period 1: LY900014 Day 1: B: SD Day 3: B: SD Period 2: Insulin lispro (Humalog) Day 1: B: SD Day 3: B: SD Period 3: LY900014 Day 1: B: SS Day 3: B: SS Period 4: Insulin lispro (Humalog) Day 1: B: SS Day 3: B: SS	Administration modes for LY900014 or Insulin lispro (Humalog) for Days 1 through 3 for breakfast: Period 1:LY900014 Day 1: B: SS Day 3: B: SS Period 2: LY900014 Day 1: B: SD Day 3: B: SD Period 3: Insulin lispro (Humalog) Day 1: B: SS Day 3: B: SS Period 4: Insulin lispro (Humalog) Day 1: B: SD Day 3: B: SD
Period Title: Period 1
STARTED	6	6	6	6
Received One Dose of Study Drug	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	6	6	6	5
COMPLETED	6	6	6	5
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Baseline
Arm/Group Description	Participants received individualized doses of LY900014 and Insulin lispro (Humalog) via CSII with various intermittent bolus doses immediately before meals, over 3 days per period.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.6 (11.4)
Sex: Female, Male (Count of Participants)
Female	6 25%
Male	18 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 100%
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	24 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Germany	24 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours(h) (AUC [0-5 h]) Following Administration of Each Study Arm With a Standard Single-wave Bolus
Description	PK: Insulin Lispro AUC(0-5h)
Time Frame	Days 1 and 3: -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of both study drugs and had evaluable PK data during the breakfast test meal.

Arm/Group Title	LY900014 SS	Insulin Lispro (Humalog) SS
Arm/Group Description	Individualized doses of LY900014 delivered via CSII with intermitted bolus dose administered as standard single-wave bolus on Day 1 and 3.	Individualized doses of Insulin lispro (Humalog) delivered via CSII with intermittent bolus dose administered as a standard single-wave bolus on Day 1 and 3.
Measure Participants	24	24
Day 1	1040 (42)	1040 (43)
Day 3	1050 (47)	1040 (48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014 SS, Insulin Lispro (Humalog) SS
	Comments	Day 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Means
	Estimated Value	1
	Confidence Interval	(2-Sided) 90%; 0.810 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY900014 SS, Insulin Lispro (Humalog) SS
	Comments	Day 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Means
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 90%; 0.817 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Following Administration of Each Study Arm With a Standard Dual-wave Bolus
Description	PK: Insulin Lispro AUC(0-5h)
Time Frame	Days 1 and 3: -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes post dose

Outcome Measure Data

Analysis Population Description

All participants who received both study drugs and had evaluable PK during the breakfast test meal.

Arm/Group Title	LY900014 SD	Insulin Lispro (Humalog) SD
Arm/Group Description	Individualized doses of LY900014 delivered via CSII with intermitted bolus dose administered as standard dual-wave bolus on Day 1 and 3.	Individualized doses of Insulin lispro (Humalog) delivered via CSII with intermitted bolus dose administered as standard dual-wave bolus on Days 1 and 3.
Measure Participants	22	22
Day 1	985 (48)	956 (46)
Day 3	1010 (53)	969 (48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014 SS, Insulin Lispro (Humalog) SS
	Comments	Day 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Means
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 90%; 0.808 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY900014 SS, Insulin Lispro (Humalog) SS
	Comments
	Type of Statistical Test	Superiority
	Comments	Day 3
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Means
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 90%; 0.820 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5h]) of Glucose Relative to Mixed Meal Tolerance Test Following Administration of Each Study Arm With a Standard Single-wave Bolus
Description	GD: Change from baseline in AUC (0-5h) of glucose relative to mixed meal tolerance test (MMTT).
Time Frame	Days 1 and 3: -30, -15, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180,195, 210, 225, 240, and 300 minutes post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of both study drugs and had evaluable GD during the breakfast test meal. Last observation carried forward (LOCF) was used for last observed glucose values prior to treatment intervention for hypoglycemic or hyperglycemic events.

Arm/Group Title	LY900014 SS	Insulin Lispro (Humalog) SS
Arm/Group Description	Individualized doses of LY900014 delivered via CSII with intermitted bolus dose administered as standard single-wave bolus on Days 1 and 3.	Individualized doses of Insulin lispro (Humalog) delivered via CSII with intermitted bolus dose administered as standard single-wave bolus on Days 1 and 3.
Measure Participants	24	24
Day 1	16.8 (182)	38.9 (186)
Day 3	140 (223)	175 (152)

4. Secondary Outcome

Title	Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Glucose Relative to MMTT Following Administration of Each Study Arm With a Standard Dual-wave Bolus
Description	GD: Change from baseline in AUC (0-5h) of glucose relative to MMTT.
Time Frame	Day 1 and 3: -30, -15, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180,195, 210, 225, 240, and 300 minutes post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of both study drugs and had evaluable GD data during the breakfast test meal. LOCF was used for last observed glucose values prior to treatment intervention for hypoglycemic or hyperglycemic events.

Arm/Group Title	LY900014 SD	Insulin Lispro (Humalog) SD
Arm/Group Description	Individualized doses of LY900014 delivered via CSII with intermitted bolus dose administered as standard dual-wave bolus on Days 1 and 3.	Individualized doses of Insulin lispro (Humalog) delivered via CSII intermitted bolus dose administered as standard dual-wave bolus on Days 1 and 3.
Measure Participants	22	22
Day 1	-1.87 (225)	106 (178)
Day 3	188 (234)	286 (221)

Adverse Events

Time Frame	Baseline through end of study (Up to 11 weeks)
Arm/Group Title	LY900014		Humalog		Open-label Humalog
Arm/Group Description	LY900014 administered via CSII		Humalog administered via CSII		Humalog administered via CSII as post-blinded study standard of care.
All Cause Mortality
	LY900014		Humalog		Open-label Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/24 (0%)
Serious Adverse Events
	LY900014		Humalog		Open-label Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	LY900014		Humalog		Open-label Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/24 (79.2%)		18/24 (75%)		10/24 (41.7%)
Ear and labyrinth disorders
Vertigo	2/24 (8.3%)	2	4/24 (16.7%)	6	1/24 (4.2%)	1
General disorders
Asthenia	1/24 (4.2%)	1	1/24 (4.2%)	2	2/24 (8.3%)	5
Fatigue	4/24 (16.7%)	5	2/24 (8.3%)	5	0/24 (0%)	0
Hunger	2/24 (8.3%)	3	1/24 (4.2%)	1	3/24 (12.5%)	6
Nervous system disorders
Headache	10/24 (41.7%)	23	9/24 (37.5%)	15	5/24 (20.8%)	5
Tremor	1/24 (4.2%)	1	2/24 (8.3%)	3	3/24 (12.5%)	4
Psychiatric disorders
Restlessness	6/24 (25%)	14	7/24 (29.2%)	20	6/24 (25%)	10
Skin and subcutaneous tissue disorders
Cold sweat	0/24 (0%)	0	1/24 (4.2%)	1	2/24 (8.3%)	2
Hyperhidrosis	3/24 (12.5%)	3	3/24 (12.5%)	3	0/24 (0%)	0
Vascular disorders
Phlebitis	2/24 (8.3%)	2	2/24 (8.3%)	2	0/24 (0%)	0

Limitations/Caveats

Rapid-Single wave bolus data is not reported as the target fasting blood glucose was not achieved, which prevented many participants from taking part in the MMTT for Day 2 resulting in unreliable data.

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.