A Study of LY900014 Formulation in Participants With Type 1 Diabetes Mellitus Using Insulin Pumps

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02703324
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 5
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

This study evaluated a blood sugar lowering insulin, LY900014, delivered by an insulin pump continuously under the skin. The study was conducted in participants with type 1 diabetes mellitus to investigate how the human body processed LY900014 and its effect on blood sugar levels when it was delivered via an insulin pump. Side effects and tolerability were be documented.

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 Continuous Subcutaneous Insulin Infusion Therapy
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 LY900014 delivered via an insulin pump as a continuous infusion under the skin with intermittent bolus doses during meals for two 3-day periods	Drug: LY900014; Administered subcutaneously (SC); Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro Insulin lispro delivered via an insulin pump as a continuous infusion under the skin with intermittent bolus doses during meals for two 3-day periods	Drug: Insulin Lispro; Administered SC

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) [Days 1 and 3: -15, 0, 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)

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) [Days 1 and 3: -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 post dose for each treatment]

   PD: AUC(0-5h) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 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 body mass index (BMI) of 18.5 to 33 kilogram per square meter (kg/m²), inclusive, at screening

• Have blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results that are 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 participating in or completed a clinical trial within the last 30 days from a clinical trial or any other type of medical research judged to be incompatible with this study

• Have previously participated or withdrawn from this study

• Have or used to have health problems, laboratory test results, blood pressure or ECG readings 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

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.	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)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02703324
• Other Study ID Numbers: 16070; I8B-FW-ITRF; 2015-004705-16
• 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	This study compared individualized doses of LY900014 (Test) to insulin lispro (Reference) when delivered via an insulin pump. The study consisted of four, three-day treatment periods, with a maximum of one week between doses in consecutive periods.

Arm/Group Title	Sequence 1, TRTR	Sequence 2, RTRT	Sequence 3, TTRR	Sequence 4, RRTT	Sequence 5, TRRT	Sequence 6, RTTR
Arm/Group Description	T = LY900014 Test. R = Insulin Lispro Reference. In each of four periods, individualized doses of study drug were delivered via an insulin pump as a continuous subcutaneous (SC) infusion with intermittent bolus doses immediately before meals for three days.	T = LY900014 Test. R = Insulin Lispro Reference. In each of four periods, individualized doses of study drug were delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses immediately before meals for three days.	T = LY900014 Test. R = Insulin Lispro Reference. In each of four periods, individualized doses of study drug were delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses immediately before meals for three days.	T = LY900014 Test. R = Insulin Lispro Reference. In each of four periods, individualized doses of study drug were delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses immediately before meals for three days.	T = LY900014 Test. R = Insulin Lispro Reference. In each of four periods, individualized doses of study drug were delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses immediately before meals for three days.	T = LY900014 Test. R = Insulin Lispro Reference. In each of four periods, individualized doses of study drug were delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses immediately before meals for three days.
Period Title: Period One
STARTED	5	5	5	5	5	5
Received Study Drug	5	5	5	5	5	5
COMPLETED	5	5	5	5	5	5
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period One
STARTED	5	5	5	5	5	5
Received Study Drug	5	5	5	5	5	5
COMPLETED	5	5	4	5	5	5
NOT COMPLETED	0	0	1	0	0	0
Period Title: Period One
STARTED	5	5	4	5	5	5
Received Study Drug	5	5	4	5	5	5
COMPLETED	5	5	4	5	5	5
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period One
STARTED	5	4	4	5	5	5
Received Study Drug	5	4	4	5	5	5
COMPLETED	5	4	4	5	5	5
NOT COMPLETED	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) delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses immediately before meals in four, three-day periods.
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.6 (12.8)
Sex: Female, Male (Count of Participants)
Female	13 43.3%
Male	17 56.7%
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])
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, 300 minutes post dose for each treatment

Outcome Measure Data

Analysis Population Description

All participants who received both study drugs and had evaluable PK data. For one participant in the Insulin Lispro - Reference group, the insulin lispro PK profile (Period Two, Day 3) was excluded from the mean PK analysis, as there was no absorption phase observed.

Arm/Group Title	Insulin Lispro - Reference	LY900014 - Test
Arm/Group Description	Individualized doses of insulin lispro delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses during meals for two 3-day periods.	Individualized doses of LY900014 delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses during meals for two 3-day periods.
Measure Participants	29	29
Day 1	918 (26)	970 (28)
Day 3	906 (30)	824 (37)

2. 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)
Description	PD: AUC(0-5h) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT)
Time Frame	Days 1 and 3: -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 post dose for each treatment

Outcome Measure Data

Analysis Population Description

All participants who received study drug and had evaluable PD data.

Arm/Group Title	Insulin Lispro - Reference	LY900014 - Test
Arm/Group Description	Individualized doses of insulin lispro delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses during meals for two three-day periods.	Individualized doses of LY900014 delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses during meals for two three-day periods.
Measure Participants	29	29
Day 1	584 (175)	567 (172)
Day 3	551 (185)	628 (210)

Adverse Events

Arm/Group Title	Insulin Lispro - Reference		LY900014 - Test		Insulin Lispro - Open Label
Arm/Group Description	Individualized doses of insulin lispro delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses during meals for two three-day periods.		Individualized doses of LY900014 delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses during meals for two three-day periods.		Individualized doses of open label insulin lispro delivered via an insulin pump as a continuous SC infusion with intermittent bolus doses between periods.
All Cause Mortality
	Insulin Lispro - Reference		LY900014 - Test		Insulin Lispro - Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Lispro - Reference		LY900014 - Test		Insulin Lispro - Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Insulin Lispro - Reference		LY900014 - Test		Insulin Lispro - Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/29 (13.8%)		3/30 (10%)		0/30 (0%)
Nervous system disorders
Headache	4/29 (13.8%)	4	3/30 (10%)	4	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.