Trial Outcomes & Findings for A Study of LY2605541 and Glargine and Exercise in Participants With Type 1 Diabetes (NCT NCT01784211)
NCT ID: NCT01784211
Last Updated: 2019-03-15
Results Overview
Venous blood samples for pharmacokinetic analysis were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
76 participants
Primary outcome timeframe
Part A: Predose and 4, 8, 12, and 24 hours postdose on Days 8, 11, and 14
Results posted on
2019-03-15
Participant Flow
Part A is 2- arm parallel open label. Part B is a crossover study with 2 treatment arms (LY2605541 \& Glargine), each treatment arm consists of 2 sequences. Sequence 1: participants received treatment on days 16,17,18,19 \& 20 with exercise on day 17. Sequence 2: participants received treatment on days 16,17,18,19, \& 20 with exercise on day 20.
Participant milestones
| Measure |
LY2605541 (Part A)
0.5 units per kilogram (U/kg) LY2605541 subcutaneously (SC) once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine (Part A)
0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
First LY2605541 + Exercise, Then LY2605541 Alone (Part B)
0.5 U/kg LY2605541 SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 17 (no exercise on Day 20).
|
First LY2605541 Alone, Then LY2605541 + Exercise (Part B)
0.5 U/kg LY2605541 SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 20 (no exercise on Day 17).
|
First Glargine + Exercise, Then Glargine Alone (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 17 (no exercise on Day 20).
|
First Glargine Alone, Then Glargine + Exercise (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 20 (no exercise on Day 17).
|
|---|---|---|---|---|---|---|
|
Part A (Days 1-15)
STARTED
|
38
|
38
|
0
|
0
|
0
|
0
|
|
Part A (Days 1-15)
Received at Least 1 Dose of Study Drug
|
37
|
38
|
0
|
0
|
0
|
0
|
|
Part A (Days 1-15)
Entered Part B
|
19
|
21
|
0
|
0
|
0
|
0
|
|
Part A (Days 1-15)
COMPLETED
|
35
|
36
|
0
|
0
|
0
|
0
|
|
Part A (Days 1-15)
NOT COMPLETED
|
3
|
2
|
0
|
0
|
0
|
0
|
|
Part B (Days 16-21)
STARTED
|
0
|
0
|
10
|
9
|
11
|
10
|
|
Part B (Days 16-21)
COMPLETED
|
0
|
0
|
10
|
9
|
11
|
10
|
|
Part B (Days 16-21)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
LY2605541 (Part A)
0.5 units per kilogram (U/kg) LY2605541 subcutaneously (SC) once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine (Part A)
0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
First LY2605541 + Exercise, Then LY2605541 Alone (Part B)
0.5 U/kg LY2605541 SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 17 (no exercise on Day 20).
|
First LY2605541 Alone, Then LY2605541 + Exercise (Part B)
0.5 U/kg LY2605541 SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 20 (no exercise on Day 17).
|
First Glargine + Exercise, Then Glargine Alone (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 17 (no exercise on Day 20).
|
First Glargine Alone, Then Glargine + Exercise (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 20 (no exercise on Day 17).
|
|---|---|---|---|---|---|---|
|
Part A (Days 1-15)
Adverse Event
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Part A (Days 1-15)
Withdrawal by Subject
|
2
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Study of LY2605541 and Glargine and Exercise in Participants With Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
LY2605541 (Part A)
n=37 Participants
0.5 units per kilogram (U/kg) LY2605541 subcutaneously (SC) once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine (Part A)
n=38 Participants
0.5 U/kg insulin Glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.2 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
42.0 years
STANDARD_DEVIATION 12.1 • n=7 Participants
|
42.6 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
36 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
37 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Part A: Predose and 4, 8, 12, and 24 hours postdose on Days 8, 11, and 14Population: Participants in Part A who received at least 1 dose of study drug and had evaluable AUCτ data.
Venous blood samples for pharmacokinetic analysis were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.
Outcome measures
| Measure |
LY2605541 (Part A)
n=37 Participants
0.5 U/kg LY2605541 SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine (Part A)
n=23 Participants
0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine + Exercise (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
Glargine (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days.
|
|---|---|---|---|---|
|
Part A: Pharmacokinetics: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUCτ) of LY2605541 and Insulin Glargine: Intra-Participant Variability
|
11.3 %CV
Interval 9.89 to 13.2
|
19.2 %CV
Interval 15.5 to 25.5
|
—
|
—
|
PRIMARY outcome
Timeframe: Part A: Predose and 4, 8, 12, and 24 hours postdose on Days 8, 11, and 14Population: Participants in Part A who received at least 1 dose of study drug and had evaluable Cmax data.
Venous blood samples for pharmacokinetic analysis were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.
Outcome measures
| Measure |
LY2605541 (Part A)
n=37 Participants
0.5 U/kg LY2605541 SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine (Part A)
n=35 Participants
0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine + Exercise (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
Glargine (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days.
|
|---|---|---|---|---|
|
Part A: Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2605541 and Insulin Glargine: Intra-Participant Variability
|
12.6 %CV
Interval 11.0 to 14.7
|
27.7 %CV
Interval 23.8 to 33.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Part A: Predose up to 24 hours postdose on Days 8, 11, and 14Population: Participants in Part A who received at least 1 dose of study drug and had evaluable Gtot data.
Glucodynamic measurements were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.
Outcome measures
| Measure |
LY2605541 (Part A)
n=37 Participants
0.5 U/kg LY2605541 SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine (Part A)
n=37 Participants
0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine + Exercise (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
Glargine (Part B)
0.5 U/kg insulin glargine SC once daily for an additional 6 days.
|
|---|---|---|---|---|
|
Part A: Pharmacodynamics: Total Amount of Glucose Infused Over the Duration of the Clamp (Gtot): Intra-Participant Variability
|
41.4 %CV
Interval 36.1 to 49.0
|
63.9 %CV
Interval 55.2 to 76.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Part B: Predose, 11 hours postdose, every 30 minutes from 16.5 to 20 hours postdose, and 24 hours postdose on Day 16 or 19Population: Participants in Part B who received at least 1 dose of study drug and had evaluable AUCτ data.
Venous blood samples for pharmacokinetic analysis were collected in Part B. Results were stratified by whether or not the participant was undergoing an exercise challenge (+ Exercise) at the time of sample collection.
Outcome measures
| Measure |
LY2605541 (Part A)
n=18 Participants
0.5 U/kg LY2605541 SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine (Part A)
n=18 Participants
0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine + Exercise (Part B)
n=10 Participants
0.5 U/kg insulin glargine SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
Glargine (Part B)
n=9 Participants
0.5 U/kg insulin glargine SC once daily for an additional 6 days.
|
|---|---|---|---|---|
|
Part B: Pharmacokinetics: AUCτ of LY2605541 and Insulin Glargine: Exercise Versus Non-Exercise
|
147000 picomoles*hour per liter (pmol*h/L)
Geometric Coefficient of Variation 25
|
130000 picomoles*hour per liter (pmol*h/L)
Geometric Coefficient of Variation 23
|
2950 picomoles*hour per liter (pmol*h/L)
Geometric Coefficient of Variation 24
|
2650 picomoles*hour per liter (pmol*h/L)
Geometric Coefficient of Variation 23
|
SECONDARY outcome
Timeframe: Part B: Predose, 11 hours postdose, every 30 minutes from 16.5 to 20 hours postdose, and 24 hours postdose on Day 16 or 19Population: Participants in Part B who received at least 1 dose of study drug and had evaluable Cmax data.
Venous blood samples for pharmacokinetic analysis were collected in Part B. Results were stratified by whether or not the participant was undergoing an exercise challenge (+ Exercise) at the time of sample collection.
Outcome measures
| Measure |
LY2605541 (Part A)
n=19 Participants
0.5 U/kg LY2605541 SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine (Part A)
n=19 Participants
0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
|
Glargine + Exercise (Part B)
n=14 Participants
0.5 U/kg insulin glargine SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
Glargine (Part B)
n=14 Participants
0.5 U/kg insulin glargine SC once daily for an additional 6 days.
|
|---|---|---|---|---|
|
Part B: Pharmacokinetics: Cmax of LY2605541 and Insulin Glargine: Exercise Versus Non-Exercise
|
11100 picomoles per liter (pmol/L)
Geometric Coefficient of Variation 27
|
6760 picomoles per liter (pmol/L)
Geometric Coefficient of Variation 28
|
166 picomoles per liter (pmol/L)
Geometric Coefficient of Variation 51
|
153 picomoles per liter (pmol/L)
Geometric Coefficient of Variation 35
|
Adverse Events
LY2605541 (Part A and Part B)
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Glargine (Part A and Part B)
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LY2605541 (Part A and Part B)
n=37 participants at risk
Part A: 0.5 U/kg LY2605541 SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
Participants who completed Part A and met certain criteria had the option of continuing to Part B.
Part B: 0.5 U/kg LY2605541 SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
Glargine (Part A and Part B)
n=38 participants at risk
Part A: 0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
Participants who completed Part A and met certain criteria had the option of continuing to Part B.
Part B: 0.5 U/kg insulin glargine SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
|---|---|---|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
2.7%
1/37 • Number of events 1
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
0.00%
0/38
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
Other adverse events
| Measure |
LY2605541 (Part A and Part B)
n=37 participants at risk
Part A: 0.5 U/kg LY2605541 SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
Participants who completed Part A and met certain criteria had the option of continuing to Part B.
Part B: 0.5 U/kg LY2605541 SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
Glargine (Part A and Part B)
n=38 participants at risk
Part A: 0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14.
Participants who completed Part A and met certain criteria had the option of continuing to Part B.
Part B: 0.5 U/kg insulin glargine SC once daily for an additional 6 days. Exercise challenge on Day 17 or 20.
|
|---|---|---|
|
Nervous system disorders
Presyncope
|
2.7%
1/37 • Number of events 1
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
5.3%
2/38 • Number of events 2
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/37
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
5.3%
2/38 • Number of events 2
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.7%
1/37 • Number of events 1
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
5.3%
2/38 • Number of events 2
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
|
Nervous system disorders
Headache
|
21.6%
8/37 • Number of events 14
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
18.4%
7/38 • Number of events 19
As per planned analysis adverse events were reported per intervention irrespective of exercise/ no exercise..
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60