A Study of LY900014 in a Medtronic Pump

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03760640
• Collaborator: (none)
• Enrollment: 42
• Locations: 2
• Arms: 2
• Actual Duration (Months): 7.6
• Patients Per Site: 21
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the study drug LY900014 to insulin lispro (Humalog) when both are delivered by the Medtronic MiniMed 670G System in adults with type 1 diabetes (T1D). The study will consist of two treatment periods of 4 weeks.

Condition or Disease	Intervention/Treatment	Phase
Type1 Diabetes Mellitus	Drug: LY900014; Drug: Insulin Lispro	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Evaluation of LY900014 in a Medtronic Pump
• Actual Study Start Date: Feb 18, 2019
• Actual Primary Completion Date: Oct 7, 2019
• Actual Study Completion Date: Oct 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 Participants received 100 units per milliliter (U/mL) of LY900014 administered via continuous subcutaneous insulin infusion (CSII) by the Medtronic MiniMed 670G insulin pump.	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro Lyumjev
Active Comparator: Insulin Lispro (Humalog) Participants received 100 U/mL of Insulin lispro (Humalog) administered via CSII by the Medtronic MiniMed 670G insulin pump.	Drug: Insulin Lispro; Administered SC; Other Names: Humalog LY275585

Outcome Measures

Primary Outcome Measures

1. Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour) [Week 2 through Week 4]

   Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.

Secondary Outcome Measures

1. Mean Sensor Glucose Value (24-Hour) [Week 2 through Week 4]

   LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.

2. Percentage of Time Spent in Auto Mode [Week 2 through Week 4]

   LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.

3. Percentage of Time With Sensor Glucose Values <54 mg/dL (24-Hour) [Week 2 through Week 4]

   LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.

4. Rate of Severe Hypoglycemic Events [Week 2 through Week 4]

   Severe hypoglycemic is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group *36525. No severe hypoglycemia was reported for this study.

5. Total Daily Insulin Dose [Week 2 through Week 4]

   LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must have been diagnosed with type 1 diabetes and have been using insulin continuously for at least 12 months

• Participants must be using an insulin pump with "rapid-acting insulin" for at least 6 months and the same "rapid acting insulin" for at least the past 30 days

• Participants must have hemoglobin A1c (HbA1c) values ≥6.0% and ≤8.0%

• Participants must have been using the MiniMed 670G insulin pump for at least the past 90 days

• Participants must use their Guardian (3) sensor at least an average of 75% of the time and remain in Auto Mode an average of 70% of the time

Exclusion Criteria:

• Participants must not have had more than 1 emergency treatment for very low blood glucose or any hospitalizations for poor glucose control (very high blood sugar or diabetic ketoacidosis) in the last 6 months

• Participants must not have significant abnormal accumulation of fat, loss of fat tissue, or scars just under the skin in areas of infusion or have a history of an infection at an infusion site within 90 days prior to screening

• Participants must not have a total daily insulin dose >100 units

• Participants must not be receiving any oral or injectable medication intended for the treatment of diabetes other than rapid-acting analog insulin via CSII in the 30 days prior to screening

• Participants must not have major problems with their heart, kidneys, liver, or have a blood disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Atlanta Diabetes Associates	Atlanta	Georgia	United States	30318
2	International Diabetes Center	Saint Louis Park	Minnesota	United States	55416

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 - Apr 13, 2019
• Statistical Analysis Plan - Oct 29, 2019

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03760640
• Other Study ID Numbers: 16917; I8B-MC-ITSM
• First Posted: Nov 30, 2018
• Last Update Posted: Oct 29, 2020
• Last Verified: Oct 15, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	Sequence 1	Sequence 2
Arm/Group Description	Participants received 100 units per milliliter (U/mL) of LY900014 or Insulin lispro delivered via continuous subcutaneous insulin infusion (CSII) using the Medtronic MiniMed 670G insulin pump. Period 1: LY900014 Period 2: Insulin Lispro (Humalog)	Participants received 100 U/mL of LY900014 or Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump. Period 1: Insulin Lispro (Humalog) Period 2: LY900014
Period Title: Period 1
STARTED	20	22
Received at Least 1 Dose of Study Drug	20	22
COMPLETED	20	22
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	20	22
COMPLETED	20	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sequence 1	Sequence 2	Total
Arm/Group Description	Participants received 100 units per milliliter (U/mL) of LY900014 or Humalog delivered via continuous subcutaneous insulin infusion (CSII) using the Medtronic MiniMed 670G insulin pump. Period 1: LY900014 Period 2: Humalog	Participants received 100 U/mL of LY900014 or Humalog delivered via CSII using the Medtronic MiniMed 670G insulin pump. Period 1: Humalog Period 2: LY900014	Total of all reporting groups
Overall Participants	20	22	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.5 (14.9)	48.1 (13.1)	47.8 (13.8)
Sex: Female, Male (Count of Participants)
Female	12 60%	15 68.2%	27 64.3%
Male	8 40%	7 31.8%	15 35.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	20 100%	22 100%	42 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 4.5%	1 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 4.5%	1 2.4%
White	20 100%	20 90.9%	40 95.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	20 100%	22 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour)
Description	Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
Time Frame	Week 2 through Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had at least one post-baseline data.

Arm/Group Title	LY900014	Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.	Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.
Measure Participants	42	42
Least Squares Mean (Standard Error) [Percentage of Time]	76.98 (0.857)	77.84 (0.857)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014, Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.339
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.86
	Confidence Interval	(2-Sided) 90%; -2.35 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Sensor Glucose Value (24-Hour)
Description	LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
Time Frame	Week 2 through Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had at least one post-baseline data.

Arm/Group Title	LY900014	Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.	Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.
Measure Participants	42	42
Least Squares Mean (Standard Error) [milligrams per deciliter (mg/dL)]	148.64 (1.193)	145.64 (1.193)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014, Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.00
	Confidence Interval	(2-Sided) 90%; 1.10 to 4.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Time Spent in Auto Mode
Description	LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
Time Frame	Week 2 through Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had at least post-baseline data.

Arm/Group Title	LY900014	Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.	Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.
Measure Participants	42	41
Least Squares Mean (Standard Error) [Percentage of Time]	91.98 (0.829)	91.42 (0.838)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014, Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.557
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 90%; -1.02 to 2.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Time With Sensor Glucose Values <54 mg/dL (24-Hour)
Description	LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
Time Frame	Week 2 through Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had at least one post-baseline data.

Arm/Group Title	LY900014	Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.	Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.
Measure Participants	42	42
Least Squares Mean (Standard Error) [Percentage of Time]	0.34 (0.067)	0.38 (0.067)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014, Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.548
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 90%; -0.15 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Rate of Severe Hypoglycemic Events
Description	Severe hypoglycemic is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group *36525. No severe hypoglycemia was reported for this study.
Time Frame	Week 2 through Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants with evaluable hypoglycemic data.

Arm/Group Title	LY900014	Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.	Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.
Measure Participants	42	42
Mean (Standard Deviation) [Events/Participant/100 Years]	0 (0)	0 (0)

6. Secondary Outcome

Title	Total Daily Insulin Dose
Description	LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
Time Frame	Week 2 through Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had at least one post-baseline data.

Arm/Group Title	LY900014	Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.	Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.
Measure Participants	42	42
Least Squares Mean (Standard Error) [Units (U)/day]	42.59 (1.023)	42.10 (1.023)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014, Insulin Lispro (Humalog)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.577
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 90%; -0.97 to 1.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up To 10 Weeks
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	LY900014		Insulin Lispro (Humalog)
Arm/Group Description	Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.		Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.
All Cause Mortality
	LY900014		Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/42 (0%)
Serious Adverse Events
	LY900014		Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	LY900014		Insulin Lispro (Humalog)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/42 (9.5%)		1/42 (2.4%)
General disorders
Infusion site pain	4/42 (9.5%)	5	1/42 (2.4%)	1

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.