A Study of LY2605541 and Glargine in Participants With Type 1 Diabetes

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01769404
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arms: 2
• Duration (Months): 10
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

This study has 2 parts. Each participant will receive a daily injection of LY2605541 during one treatment period and a daily injection of insulin glargine during one treatment period. Each treatment period is 2 to 3 weeks and is followed by a procedure to lower blood sugar levels to see how the body recovers after each treatment.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Biological: LY2605541; Biological: Insulin Glargine	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Evaluation of the Counter-Regulatory Response to Hypoglycaemia Following LY2605541 Administration Compared to Insulin Glargine in Patients With Type 1 Diabetes Mellitus
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2605541 Stable dose of LY2605541 (0.2 to 0.6 units per kilogram [U/kg]) administered subcutaneously (SQ) once daily for at least 14 days in 1 of 2 treatment periods. Dose based on prestudy basal insulin dosing regimen.	Biological: LY2605541
Active Comparator: Insulin Glargine Stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days in 1 of 2 treatment periods. Dose based on prestudy basal insulin dosing regimen.	Biological: Insulin Glargine

Outcome Measures

Primary Outcome Measures

1. Concentration of Epinephrine [30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp]

   Epinephrine levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at blood glucose (BG) level attainment and +10, 20, and 30 minutes were averaged for the BG nadir value.

Secondary Outcome Measures

1. Amount of Glucose Required to Reach Blood Glucose (BG) of 72 mg/dL [30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp]

   The amount of infused glucose required to reach BG of 72 milligrams per deciliter (mg/dL) is presented.

2. Amount of Glucose Required to Maintain BG of 72 mg/dL [30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp]

   The amount of infused glucose required to maintain BG of 72 mg/dL for 1 hour is presented.

3. Concentration of Cortisol [30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp]

   Cortisol levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at BG level attainment and +30 minutes were averaged for the BG nadir value.

4. Concentration of Glucagon [30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp]

   Glucagon levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at BG level attainment and +30 minutes were averaged for the BG nadir value.

5. Concentration of Growth Hormone [30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp]

   Growth hormone levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at BG level attainment and +30 minutes were averaged for the BG nadir value.

6. Concentration of Norepinephrine [30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp]

   Norepinephrine values are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at BG level attainment and +10, 20, and 30 minutes were averaged for the BG nadir value.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Type 1 diabetic for more than 1 year with glycated hemoglobin (HbA1c) less than 9%

• Otherwise fit and healthy

• Nonsmoker

Exclusion Criteria:

• Taking medication or supplements other than insulin to control diabetes

• Suffered a hypoglycemic event in the last 12 months that required hospitalization or has poor awareness of hypoglycemia

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 from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Neuss		Germany	41460

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: NCT01769404
• Other Study ID Numbers: 14870; I2R-MC-BIDM
• First Posted: Jan 16, 2013
• Last Update Posted: Jun 24, 2019
• Last Verified: Mar 1, 2019

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

Study Results

Participant Flow

Pre-assignment Detail	As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

Arm/Group Title	Cohort 1 (LY2605541, Then Insulin Glargine)	Cohort 2 (Insulin Glargine, Then LY2605541)
Arm/Group Description	Participants received a stable dose of 0.2 to 0.6 U/kg LY2605541, administered subcutaneously (SQ), once daily for 14 days in Treatment Period 1, followed by a stable dose of 0.2 to 0.6 U/kg insulin glargine, administered SQ, once daily for 14 days in Treatment Period 2.	Participants received a stable dose of 0.2 to 0.6 U/kg insulin glargine, administered SQ, once daily for 14 days in Treatment Period 1, followed by a stable dose of 0.2 to 0.6 U/kg LY2605541, administered SQ, once daily for 14 days in Treatment Period 2.
Period Title: Treatment Period 1
STARTED	12	13
Received at Least 1 Dose of Study Drug	9	13
COMPLETED	7	13
NOT COMPLETED	5	0
Period Title: Treatment Period 1
STARTED	7	13
COMPLETED	0	13
NOT COMPLETED	7	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants who received at least 1 dose of study drug.
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.1 (10.7)
Sex: Female, Male (Count of Participants)
Female	4 18.2%
Male	18 81.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	22 100%
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	22 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Germany	22 100%

Outcome Measures

1. Primary Outcome

Title	Concentration of Epinephrine
Description	Epinephrine levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at blood glucose (BG) level attainment and +10, 20, and 30 minutes were averaged for the BG nadir value.
Time Frame	30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp

Outcome Measure Data

Analysis Population Description

All participants in Cohort 2 who received at least 1 dose of study drug with evaluable epinephrine data. As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

Arm/Group Title	LY2605541	Insulin Glargine
Arm/Group Description	Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.	Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.
Measure Participants	13	13
Baseline	157.2 (90.9)	196.5 (207.0)
BG nadir	607.5 (281.0)	525.2 (305.4)

2. Secondary Outcome

Title	Amount of Glucose Required to Reach Blood Glucose (BG) of 72 mg/dL
Description	The amount of infused glucose required to reach BG of 72 milligrams per deciliter (mg/dL) is presented.
Time Frame	30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp

Outcome Measure Data

Analysis Population Description

All participants in Cohort 2 who received at least 1 dose of study drug with evaluable BG data. As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

Arm/Group Title	LY2605541	Insulin Glargine
Arm/Group Description	Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.	Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.
Measure Participants	13	13
Geometric Mean (Geometric Coefficient of Variation) [milligrams (mg)]	11600 (37)	12700 (43)

3. Secondary Outcome

Title	Amount of Glucose Required to Maintain BG of 72 mg/dL
Description	The amount of infused glucose required to maintain BG of 72 mg/dL for 1 hour is presented.
Time Frame	30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp

Outcome Measure Data

Analysis Population Description

All participants in Cohort 2 who received at least 1 dose of study drug with evaluable BG data. As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

Arm/Group Title	LY2605541	Insulin Glargine
Arm/Group Description	Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.	Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.
Measure Participants	13	13
Geometric Mean (Geometric Coefficient of Variation) [mg]	15400 (34)	15900 (37)

4. Secondary Outcome

Title	Concentration of Cortisol
Description	Cortisol levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at BG level attainment and +30 minutes were averaged for the BG nadir value.
Time Frame	30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp

Outcome Measure Data

Analysis Population Description

All participants in Cohort 2 who received at least 1 dose of study drug with evaluable cortisol data. As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

Arm/Group Title	LY2605541	Insulin Glargine
Arm/Group Description	Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.	Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.
Measure Participants	13	13
Baseline	206.7 (75.4)	260.0 (92.4)
BG nadir	337.3 (121.2)	333.8 (74.0)

5. Secondary Outcome

Title	Concentration of Glucagon
Description	Glucagon levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at BG level attainment and +30 minutes were averaged for the BG nadir value.
Time Frame	30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp

Outcome Measure Data

Analysis Population Description

All participants in Cohort 2 who received at least 1 dose of study drug with evaluable glucagon data. As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

Arm/Group Title	LY2605541	Insulin Glargine
Arm/Group Description	Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.	Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.
Measure Participants	13	13
Baseline	8.02 (2.88)	5.28 (2.46)
BG nadir	5.89 (2.82)	4.98 (2.79)

6. Secondary Outcome

Title	Concentration of Growth Hormone
Description	Growth hormone levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at BG level attainment and +30 minutes were averaged for the BG nadir value.
Time Frame	30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp

Outcome Measure Data

Analysis Population Description

All participants in Cohort 2 who received at least 1 dose of study drug with evaluable growth hormone data. As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

Arm/Group Title	LY2605541	Insulin Glargine
Arm/Group Description	Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.	Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.
Measure Participants	13	13
Baseline	1.0816 (2.5527)	1.3948 (1.3981)
BG nadir	6.8752 (6.7187)	8.0114 (9.9621)

7. Secondary Outcome

Title	Concentration of Norepinephrine
Description	Norepinephrine values are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at BG level attainment and +10, 20, and 30 minutes were averaged for the BG nadir value.
Time Frame	30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp

Outcome Measure Data

Analysis Population Description

All participants in Cohort 2 who received at least 1 dose of study drug with evaluable norepinephrine data. As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

Arm/Group Title	LY2605541	Insulin Glargine
Arm/Group Description	Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.	Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days. Dose based on prestudy basal insulin dosing regimen.
Measure Participants	13	13
Baseline	1004.2 (358.2)	1139.8 (603.2)
BG nadir	1235.8 (422.8)	1434.8 (933.3)

Adverse Events

Arm/Group Title	Cohort 1: 0.2-0.6 U/kg LY2605541		Cohort 1: 0.2-0.6 U/kg Insulin Glargine		Cohort 2: 0.2-0.6 U/kg LY2605541		Cohort 2: 0.2-0.6 U/kg Insulin Glargine
Arm/Group Description	Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days in Treatment Period 1 or 2. Dose based on prestudy basal insulin dosing regimen.		Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days in Treatment Period 1 or 2. Dose based on prestudy basal insulin dosing regimen.		Participants received a stable dose of LY2605541 (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days in Treatment Period 1 or 2. Dose based on prestudy basal insulin dosing regimen.		Participants received a stable dose of insulin glargine (0.2 to 0.6 U/kg) administered SQ once daily for at least 14 days in Treatment Period 1 or 2. Dose based on prestudy basal insulin dosing regimen.
All Cause Mortality
	Cohort 1: 0.2-0.6 U/kg LY2605541		Cohort 1: 0.2-0.6 U/kg Insulin Glargine		Cohort 2: 0.2-0.6 U/kg LY2605541		Cohort 2: 0.2-0.6 U/kg Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1: 0.2-0.6 U/kg LY2605541		Cohort 1: 0.2-0.6 U/kg Insulin Glargine		Cohort 2: 0.2-0.6 U/kg LY2605541		Cohort 2: 0.2-0.6 U/kg Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/7 (0%)		0/13 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: 0.2-0.6 U/kg LY2605541		Cohort 1: 0.2-0.6 U/kg Insulin Glargine		Cohort 2: 0.2-0.6 U/kg LY2605541		Cohort 2: 0.2-0.6 U/kg Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		3/7 (42.9%)		1/13 (7.7%)		3/13 (23.1%)
Gastrointestinal disorders
Abdominal pain	0/9 (0%)	0	0/7 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Vomiting	0/9 (0%)	0	0/7 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Infections and infestations
Influenza	0/9 (0%)	0	1/7 (14.3%)	1	0/13 (0%)	0	0/13 (0%)	0
Nervous system disorders
Headache	1/9 (11.1%)	1	2/7 (28.6%)	3	0/13 (0%)	0	1/13 (7.7%)	1
Presyncope	0/9 (0%)	0	0/7 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Vascular disorders
Phlebitis	0/9 (0%)	0	0/7 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1

Limitations/Caveats

As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.

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.