Trial Outcomes & Findings for A Study to Compare LY2963016 and US-approved Lantus® After Single Dose Administration to Healthy Participants (NCT NCT01688635)
NCT ID: NCT01688635
Last Updated: 2014-10-07
Results Overview
The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
91 participants
Primary outcome timeframe
30 minutes predose up to 24 hours postdose in all treatment periods
Results posted on
2014-10-07
Participant Flow
The study comprised 2 sequences with 4 treatment periods. Participants were randomly assigned to 1 of the 2 sequences.
Participant milestones
| Measure |
LY/Lantus/LY/Lantus
A single 0.5-units/kilogram (U/kg) dose of LY2963016 (LY) administered subcutaneously during Periods 1 and 3.
A single 0.5-U/kg dose of US-approved Lantus (Lantus) administered subcutaneously during Periods 2 and 4.
There was at least a 7-day washout between treatment periods.
|
Lantus/LY/Lantus/LY
A single 0.5-U/kg dose of US-approved Lantus administered subcutaneously during Periods 1 and 3.
A single 0.5-U/kg dose of LY2963016 administered subcutaneously during Periods 2 and 4.
There was at least a 7-day washout between treatment periods.
|
|---|---|---|
|
Period 1
STARTED
|
45
|
46
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
45
|
46
|
|
Period 1
COMPLETED
|
45
|
46
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Washout 1
STARTED
|
45
|
46
|
|
Washout 1
COMPLETED
|
44
|
44
|
|
Washout 1
NOT COMPLETED
|
1
|
2
|
|
Period 2
STARTED
|
44
|
44
|
|
Period 2
COMPLETED
|
44
|
44
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
|
Washout 2
STARTED
|
44
|
44
|
|
Washout 2
COMPLETED
|
41
|
42
|
|
Washout 2
NOT COMPLETED
|
3
|
2
|
|
Period 3
STARTED
|
41
|
42
|
|
Period 3
COMPLETED
|
41
|
42
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
|
Washout 3
STARTED
|
41
|
42
|
|
Washout 3
COMPLETED
|
40
|
42
|
|
Washout 3
NOT COMPLETED
|
1
|
0
|
|
Period 4
STARTED
|
40
|
42
|
|
Period 4
COMPLETED
|
40
|
42
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
LY/Lantus/LY/Lantus
A single 0.5-units/kilogram (U/kg) dose of LY2963016 (LY) administered subcutaneously during Periods 1 and 3.
A single 0.5-U/kg dose of US-approved Lantus (Lantus) administered subcutaneously during Periods 2 and 4.
There was at least a 7-day washout between treatment periods.
|
Lantus/LY/Lantus/LY
A single 0.5-U/kg dose of US-approved Lantus administered subcutaneously during Periods 1 and 3.
A single 0.5-U/kg dose of LY2963016 administered subcutaneously during Periods 2 and 4.
There was at least a 7-day washout between treatment periods.
|
|---|---|---|
|
Washout 1
Withdrawal by Subject
|
1
|
0
|
|
Washout 1
Adverse Event
|
0
|
1
|
|
Washout 1
Physician Decision
|
0
|
1
|
|
Washout 2
Physician Decision
|
1
|
0
|
|
Washout 2
Withdrawal by Subject
|
1
|
0
|
|
Washout 2
Sponsor Decision
|
1
|
2
|
|
Washout 3
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
A Study to Compare LY2963016 and US-approved Lantus® After Single Dose Administration to Healthy Participants
Baseline characteristics by cohort
| Measure |
LY2963016 and US-approved Lantus
n=91 Participants
Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study; Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study. There was at least a 7-day washout between treatment periods.
|
|---|---|
|
Age, Continuous
|
32.7 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
85 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
90 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
91 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 30 minutes predose up to 24 hours postdose in all treatment periodsPopulation: Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate AUC(0-24). Participants were analyzed based on the treatment they received.
The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured.
Outcome measures
| Measure |
LY2963016
n=87 Participants
Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study. There was at least a 7-day washout between treatment periods.
|
US-approved Lantus
n=89 Participants
Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study.
There was at least a 7-day washout between treatment periods.
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus
|
1720 picomoles*hour/liter (pmol*h/L)
Geometric Coefficient of Variation 42
|
1900 picomoles*hour/liter (pmol*h/L)
Geometric Coefficient of Variation 35
|
PRIMARY outcome
Timeframe: 30 minutes predose up to 24 hours postdose in all treatment periodsPopulation: Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate Cmax. Participants were analyzed based on the treatment they received
Outcome measures
| Measure |
LY2963016
n=88 Participants
Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study. There was at least a 7-day washout between treatment periods.
|
US-approved Lantus
n=89 Participants
Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study.
There was at least a 7-day washout between treatment periods.
|
|---|---|---|
|
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus
|
103 picomoles/liter (pmol/L)
Geometric Coefficient of Variation 41
|
111 picomoles/liter (pmol/L)
Geometric Coefficient of Variation 34
|
SECONDARY outcome
Timeframe: 30 minutes predose up to 24 hours postdose in all treatment periodsPopulation: Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data to calculate Rmax. Participants were analyzed based on the treatment they received.
Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
Outcome measures
| Measure |
LY2963016
n=88 Participants
Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study. There was at least a 7-day washout between treatment periods.
|
US-approved Lantus
n=88 Participants
Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study.
There was at least a 7-day washout between treatment periods.
|
|---|---|---|
|
Maximum Glucose Infusion Rate (Rmax)
|
2.12 milligrams/kilograms/minute (mg/kg/min)
Geometric Coefficient of Variation 54
|
2.27 milligrams/kilograms/minute (mg/kg/min)
Geometric Coefficient of Variation 58
|
SECONDARY outcome
Timeframe: 30 minutes predose up to 24 hours postdose in all treatment periodsPopulation: Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data to calculate Gtot. Participants were analyzed based on the treatment they received.
Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
Outcome measures
| Measure |
LY2963016
n=88 Participants
Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study. There was at least a 7-day washout between treatment periods.
|
US-approved Lantus
n=88 Participants
Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study.
There was at least a 7-day washout between treatment periods.
|
|---|---|---|
|
Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure
|
1670 milligrams/kilogram (mg/kg)
Geometric Coefficient of Variation 60
|
1820 milligrams/kilogram (mg/kg)
Geometric Coefficient of Variation 74
|
Adverse Events
LY2963016
Serious events: 0 serious events
Other events: 42 other events
Deaths: 0 deaths
US-approved Lantus
Serious events: 0 serious events
Other events: 42 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LY2963016
n=89 participants at risk
Single 0.5 units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study.
There was at least a 7-day washout between the treatment periods.
|
US-approved Lantus
n=90 participants at risk
Single 0.5 U/kg dose of US-approved Lantus administered subcutaneously twice during the study.
There was at least a 7-day washout between the treatment periods.
|
|---|---|---|
|
General disorders
Catheter site haematoma
|
11.2%
10/89 • Number of events 11 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
10.0%
9/90 • Number of events 11 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
|
General disorders
Catheter site pain
|
5.6%
5/89 • Number of events 5 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
6.7%
6/90 • Number of events 6 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
|
General disorders
Catheter site swelling
|
10.1%
9/89 • Number of events 10 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
7.8%
7/90 • Number of events 7 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
|
General disorders
Infusion site pain
|
4.5%
4/89 • Number of events 4 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
4.4%
4/90 • Number of events 5 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
|
General disorders
Infusion site swelling
|
2.2%
2/89 • Number of events 2 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
5.6%
5/90 • Number of events 6 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
|
General disorders
Pyrexia
|
4.5%
4/89 • Number of events 4 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
1.1%
1/90 • Number of events 1 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
2.2%
2/89 • Number of events 2 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
4.4%
4/90 • Number of events 5 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
|
Nervous system disorders
Headache
|
3.4%
3/89 • Number of events 3 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
8.9%
8/90 • Number of events 9 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
4.5%
4/89 • Number of events 4 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
3.3%
3/90 • Number of events 3 • Randomization to study completion
Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
|
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