Trial Outcomes & Findings for A Study of LY2605541 and Glargine in Participants With Type 1 Diabetes (NCT NCT01769404)
NCT ID: NCT01769404
Last Updated: 2019-06-24
Results Overview
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.
COMPLETED
PHASE1
25 participants
30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-Clamp
2019-06-24
Participant Flow
As per protocol amendment, no participants in cohort 1 were analyzed and only cohort 2 participants were analyzed for efficacy.
Participant milestones
| Measure |
Cohort 1 (LY2605541, Then Insulin Glargine)
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.
|
Cohort 2 (Insulin Glargine, Then LY2605541)
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.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
12
|
13
|
|
Treatment Period 1
Received at Least 1 Dose of Study Drug
|
9
|
13
|
|
Treatment Period 1
COMPLETED
|
7
|
13
|
|
Treatment Period 1
NOT COMPLETED
|
5
|
0
|
|
Treatment Period 2
STARTED
|
7
|
13
|
|
Treatment Period 2
COMPLETED
|
0
|
13
|
|
Treatment Period 2
NOT COMPLETED
|
7
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1 (LY2605541, Then Insulin Glargine)
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.
|
Cohort 2 (Insulin Glargine, Then LY2605541)
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.
|
|---|---|---|
|
Treatment Period 1
Did not meet eligibility criteria
|
1
|
0
|
|
Treatment Period 1
Withdrawal by Subject
|
3
|
0
|
|
Treatment Period 1
Sponsor decision
|
1
|
0
|
|
Treatment Period 2
Sponsor decision
|
7
|
0
|
Baseline Characteristics
A Study of LY2605541 and Glargine in Participants With Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
All Participants
n=22 Participants
All participants who received at least 1 dose of study drug.
|
|---|---|
|
Age, Continuous
|
41.1 years
STANDARD_DEVIATION 10.7 • n=93 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
Germany
|
22 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-ClampPopulation: 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.
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.
Outcome measures
| Measure |
LY2605541
n=13 Participants
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.
|
Insulin Glargine
n=13 Participants
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.
|
|---|---|---|
|
Concentration of Epinephrine
Baseline
|
157.2 picomole per liter (pmol/L)
Standard Deviation 90.9
|
196.5 picomole per liter (pmol/L)
Standard Deviation 207.0
|
|
Concentration of Epinephrine
BG nadir
|
607.5 picomole per liter (pmol/L)
Standard Deviation 281.0
|
525.2 picomole per liter (pmol/L)
Standard Deviation 305.4
|
SECONDARY outcome
Timeframe: 30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-ClampPopulation: 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.
The amount of infused glucose required to reach BG of 72 milligrams per deciliter (mg/dL) is presented.
Outcome measures
| Measure |
LY2605541
n=13 Participants
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.
|
Insulin Glargine
n=13 Participants
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.
|
|---|---|---|
|
Amount of Glucose Required to Reach Blood Glucose (BG) of 72 mg/dL
|
11600 milligrams (mg)
Geometric Coefficient of Variation 37
|
12700 milligrams (mg)
Geometric Coefficient of Variation 43
|
SECONDARY outcome
Timeframe: 30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-ClampPopulation: 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.
The amount of infused glucose required to maintain BG of 72 mg/dL for 1 hour is presented.
Outcome measures
| Measure |
LY2605541
n=13 Participants
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.
|
Insulin Glargine
n=13 Participants
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.
|
|---|---|---|
|
Amount of Glucose Required to Maintain BG of 72 mg/dL
|
15400 mg
Geometric Coefficient of Variation 34
|
15900 mg
Geometric Coefficient of Variation 37
|
SECONDARY outcome
Timeframe: 30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-ClampPopulation: 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.
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.
Outcome measures
| Measure |
LY2605541
n=13 Participants
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.
|
Insulin Glargine
n=13 Participants
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.
|
|---|---|---|
|
Concentration of Cortisol
Baseline
|
206.7 nanomole per liter (nmol/L)
Standard Deviation 75.4
|
260.0 nanomole per liter (nmol/L)
Standard Deviation 92.4
|
|
Concentration of Cortisol
BG nadir
|
337.3 nanomole per liter (nmol/L)
Standard Deviation 121.2
|
333.8 nanomole per liter (nmol/L)
Standard Deviation 74.0
|
SECONDARY outcome
Timeframe: 30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-ClampPopulation: 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.
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.
Outcome measures
| Measure |
LY2605541
n=13 Participants
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.
|
Insulin Glargine
n=13 Participants
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.
|
|---|---|---|
|
Concentration of Glucagon
Baseline
|
8.02 pmol/L
Standard Deviation 2.88
|
5.28 pmol/L
Standard Deviation 2.46
|
|
Concentration of Glucagon
BG nadir
|
5.89 pmol/L
Standard Deviation 2.82
|
4.98 pmol/L
Standard Deviation 2.79
|
SECONDARY outcome
Timeframe: 30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-ClampPopulation: 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.
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.
Outcome measures
| Measure |
LY2605541
n=13 Participants
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.
|
Insulin Glargine
n=13 Participants
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.
|
|---|---|---|
|
Concentration of Growth Hormone
Baseline
|
1.0816 micrograms per liter (µg/L)
Standard Deviation 2.5527
|
1.3948 micrograms per liter (µg/L)
Standard Deviation 1.3981
|
|
Concentration of Growth Hormone
BG nadir
|
6.8752 micrograms per liter (µg/L)
Standard Deviation 6.7187
|
8.0114 micrograms per liter (µg/L)
Standard Deviation 9.9621
|
SECONDARY outcome
Timeframe: 30, 15, and 0 minutes Preclamp; 10, 20, and 30 minutes Post-ClampPopulation: 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.
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.
Outcome measures
| Measure |
LY2605541
n=13 Participants
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.
|
Insulin Glargine
n=13 Participants
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.
|
|---|---|---|
|
Concentration of Norepinephrine
Baseline
|
1004.2 pmol/L
Standard Deviation 358.2
|
1139.8 pmol/L
Standard Deviation 603.2
|
|
Concentration of Norepinephrine
BG nadir
|
1235.8 pmol/L
Standard Deviation 422.8
|
1434.8 pmol/L
Standard Deviation 933.3
|
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
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1: 0.2-0.6 U/kg LY2605541
n=9 participants at risk
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.
|
Cohort 1: 0.2-0.6 U/kg Insulin Glargine
n=7 participants at risk
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.
|
Cohort 2: 0.2-0.6 U/kg LY2605541
n=13 participants at risk
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.
|
Cohort 2: 0.2-0.6 U/kg Insulin Glargine
n=13 participants at risk
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.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/13
|
7.7%
1/13 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/9
|
0.00%
0/7
|
7.7%
1/13 • Number of events 1
|
0.00%
0/13
|
|
Infections and infestations
Influenza
|
0.00%
0/9
|
14.3%
1/7 • Number of events 1
|
0.00%
0/13
|
0.00%
0/13
|
|
Nervous system disorders
Headache
|
11.1%
1/9 • Number of events 1
|
28.6%
2/7 • Number of events 3
|
0.00%
0/13
|
7.7%
1/13 • Number of events 1
|
|
Nervous system disorders
Presyncope
|
0.00%
0/9
|
0.00%
0/7
|
7.7%
1/13 • Number of events 1
|
0.00%
0/13
|
|
Vascular disorders
Phlebitis
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/13
|
7.7%
1/13 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60