A Study of 2 Different Formulations of Insulin Lispro in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02111083
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 12.6

Study Details

Study Description

Brief Summary

The study involves 4 injections of insulin lispro and its purpose is to:

• Determine if 2 formulations of insulin lispro are treated by the body in a similar way.

• Compare how the 2 formulations of insulin lispro affect blood sugar level.

• Determine the safety of each insulin lispro formulations and any side effects that might be associated with them when given to healthy participants. The study is expected to last up to approximately 9 weeks for each participant.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Biological: Insulin Lispro	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Evaluation of the Bioequivalence of Two Formulations of Insulin Lispro in Healthy Subjects
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Insulin Lispro A Insulin Lispro A 20 units (U) of strength 200 units per milliliter (U/mL) (U-200)administered subcutaneously (SC) once in two of four study periods.(Two doses of test [T]).	Biological: Insulin Lispro; LY275585 administered SC.
Experimental: Insulin Lispro B Insulin Lispro B 20 units (U) of strength 100 U/mL (U-100) administered SC once in two of four study periods.(Two doses of reference [R]).	Biological: Insulin Lispro; LY275585 administered SC.

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Zero to Time of Return to Baseline (AUC0-tlast) [Day 1, predose through 8 hours post dose in each period.]

2. Pharmacokinetic Parameter: Maximum Serum Insulin Concentration (Cmax) [Day 1, predose through 8 hours post dose in each period]

3. Pharmacokinetic Parameter: Area Under the Curve(AUC) [Zero to infinity [AUC(0-∞)]]

Secondary Outcome Measures

1. Pharmacokinetic Parameter: Time of Maximum Observed Serum Concentration (Tmax) [Day 1, predose through 8 hours post dose in each period.]

2. Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot) [Day1, predose through 8 hours post dose in each period.]

   The total amount of glucose infused during the euglycemic clamp procedure.

3. Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax) [Day 1, predose through 8 hours post dose in each period.]

   The maximum observed glucose infusion rate during the euglycemic clamp procedure.

4. Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax) [Day 1, predose through 8 hours post dose in each period.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Are healthy males or females

• Body mass index (BMI) between 18.5 and 29.9 kilogram per meter squared (kg/m^2)

• Are nonsmokers

• Have normal blood pressure and pulse rate, a normal electrocardiogram (ECG), and clinical laboratory test results within normal reference range at screening.

Exclusion Criteria:

• History of first-degree relatives known to have diabetes mellitus

• Evidence of significant active neuropsychiatric disease

• Evidence of an acute infection with fever or infectious disease

• Intend to use over-the-counter or prescription medication (apart from vitamin/mineral supplements, occasional paracetamol, or birth control methods).

• Have used systemic glucocorticoids within 3 months prior to entry into the study.

• Have donated blood of 1 unit or more within the last 3 months prior to study entry

• Excessive alcohol intake

• Have a fasting venous blood glucose (fasting blood glucose [FBG], plasma) >6 millimoles per liter (mmol/L) at screening

• Have positive hepatitis B surface antigen.

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.	Singapore		Singapore	117597

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: NCT02111083
• Other Study ID Numbers: 15418; F3Z-EW-IOQM
• First Posted: Apr 10, 2014
• Last Update Posted: May 21, 2015
• Last Verified: May 1, 2015

• Additional relevant MeSH terms: Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	Insulin Lispro Dosing Sequence TRTR	Insulin Lispro Dosing Sequence RTRT
Arm/Group Description	Each subject was administered insulin lispro A 20 units (U) of strength 200 units per milliliter (U/mL) (U-200) (test [T] on 2 occasions) and insulin lispro B 20 units (U) of strength 100 U/mL (U-100) (reference [R] on 2 occasions).Subjects were randomly assigned to dosing sequences TRTR.	Each subject was administered insulin lispro A 20 units (U) of strength 200 units per milliliter (U/mL) (U-200) (test [T] on 2 occasions) and insulin lispro B 20 units (U) of strength 100 U/mL (U-100) (reference [R] on 2 occasions).Subjects were randomly assigned to dosing sequences RTRT.
Period Title: First Intervention (1 Day)
STARTED	19	19
COMPLETED	19	19
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day)
STARTED	19	19
COMPLETED	19	19
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day)
STARTED	19	19
COMPLETED	19	19
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day)
STARTED	19	19
COMPLETED	19	19
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day)
STARTED	19	19
COMPLETED	19	19
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day)
STARTED	19	19
COMPLETED	18	18
NOT COMPLETED	1	1
Period Title: First Intervention (1 Day)
STARTED	18	18
COMPLETED	18	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Insulin Lispro Dosing Sequence TRTR	Insulin Lispro Dosing Sequence RTRT	Total
Arm/Group Description	Each subject was administered insulin lispro A U-200 (test [T] on 2 occasions) and insulin lispro B U-100(reference [R] on 2 occasions).Subjects were randomly assigned to dosing sequences TRTR.	Each subject was administered insulin lispro A U-200 (test [T] on 2 occasions) and insulin lispro B U-100 (reference [R] on 2 occasions). Subjects were randomly assigned to dosing sequences RTRT.	Total of all reporting groups
Overall Participants	19	19	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.9 (6.1)	30.4 (8.2)	31.7 (7.2)
Sex: Female, Male (Count of Participants)
Female	2 10.5%	1 5.3%	3 7.9%
Male	17 89.5%	18 94.7%	35 92.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	19 100%	19 100%	38 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Singapore	19 100%	19 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Zero to Time of Return to Baseline (AUC0-tlast)
Time Frame	Day 1, predose through 8 hours post dose in each period.

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable pharmacokinetic (PK) data.

Arm/Group Title	Insulin Lispro A	Insulin Lispro B
Arm/Group Description	Insulin Lispro A U-200 administered subcutaneously (SC) once in two of four study periods. (Two doses of test [T]).	Insulin Lispro B U-100 administered SC once in two of four study periods. (Two doses of reference [R]).
Measure Participants	38	38
Geometric Mean (Geometric Coefficient of Variation) [picomole*hour/liter (pmol*h/L)]	2200 (16)	2230 (17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Lispro A, Insulin Lispro B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least square means
	Estimated Value	0.986
	Confidence Interval	(2-Sided) 90%; 0.965 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Pharmacokinetic Parameter: Maximum Serum Insulin Concentration (Cmax)
Time Frame	Day 1, predose through 8 hours post dose in each period

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable PK data.

Arm/Group Title	Insulin Lispro A	Insulin Lispro B
Arm/Group Description	Insulin Lispro A U-200 administered subcutaneously (SC) once in two of four study periods. (Two doses of test [T]).	Insulin Lispro B U-100 administered SC once in two of four study periods. (Two doses of reference [R]).
Measure Participants	38	38
Geometric Mean (Geometric Coefficient of Variation) [picomole/liter (pmol/L)]	744 (38)	851 (38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Lispro A, Insulin Lispro B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least square means
	Estimated Value	0.872
	Confidence Interval	(2-Sided) 90%; 0.828 to 0.919
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Pharmacokinetic Parameter: Time of Maximum Observed Serum Concentration (Tmax)
Time Frame	Day 1, predose through 8 hours post dose in each period.

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable PK data.

Arm/Group Title	Insulin Lispro A	Insulin Lispro B
Arm/Group Description	Insulin Lispro A U-200 administered subcutaneously (SC) once in two of four study periods. (Two doses of test [T]).	Insulin Lispro B U-100 administered SC once in two of four study periods. (Two doses of reference [R]).
Measure Participants	38	38
Median (Full Range) [hours]	1	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Lispro A, Insulin Lispro B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 90%; 0 to 0.375
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot)
Description	The total amount of glucose infused during the euglycemic clamp procedure.
Time Frame	Day1, predose through 8 hours post dose in each period.

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable pharmacodynamic(PD) data.

Arm/Group Title	Insulin Lispro A	Insulin Lispro B
Arm/Group Description	Insulin Lispro A U-200 administered subcutaneously (SC) once in two of four study periods. (Two doses of test [T]).	Insulin Lispro B U-100 administered SC once in two of four study periods. (Two doses of reference [R]).
Measure Participants	38	38
Geometric Mean (Geometric Coefficient of Variation) [grams (g)]	120 (31)	120 (33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Lispro A, Insulin Lispro B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least square means
	Estimated Value	0.986
	Confidence Interval	(2-Sided) 90%; 0.954 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax)
Description	The maximum observed glucose infusion rate during the euglycemic clamp procedure.
Time Frame	Day 1, predose through 8 hours post dose in each period.

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable PD data.

Arm/Group Title	Insulin Lispro A	Insulin Lispro B
Arm/Group Description	Insulin Lispro A U-200 administered subcutaneously (SC) once in two of four study periods. (Two doses of test [T]).	Insulin Lispro B U-100 administered SC once in two of four study periods. (Two doses of reference [R]).
Measure Participants	38	38
Geometric Mean (Geometric Coefficient of Variation) [milligrams per minute (mg/min)]	503 (36)	526 (36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Lispro A, Insulin Lispro B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least square means
	Estimated Value	0.950
	Confidence Interval	(2-Sided) 90%; 0.901 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax)
Time Frame	Day 1, predose through 8 hours post dose in each period.

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable PD data.

Arm/Group Title	Insulin Lispro A	Insulin Lispro B
Arm/Group Description	Insulin Lispro A U-200 administered subcutaneously (SC) once in two of four study periods. (Two doses of test [T]).	Insulin Lispro B U-100 administered SC once in two of four study periods. (Two doses of reference [R]).
Measure Participants	38	38
Geometric Mean (Geometric Coefficient of Variation) [hours]	2.71 (52)	2.32 (52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Lispro A, Insulin Lispro B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of least squares means
	Estimated Value	0.424
	Confidence Interval	(2-Sided) 90%; 0.164 to 0.685
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Primary Outcome

Title	Pharmacokinetic Parameter: Area Under the Curve(AUC)
Time Frame	Zero to infinity [AUC(0-∞)]

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable PK data.

Arm/Group Title	Insulin Lispro A	Insulin Lispro B
Arm/Group Description	Insulin Lispro A U-200 administered subcutaneously (SC) once in two of four study periods. (Two doses of test [T]).	Insulin Lispro B U-100 administered SC once in two of four study periods. (Two doses of reference [R]).
Measure Participants	38	38
Geometric Mean (Geometric Coefficient of Variation) [picomole*hour/liter (pmol*h/L)]	2330 (15)	2360 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Lispro A, Insulin Lispro B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least square means
	Estimated Value	0.992
	Confidence Interval	(2-Sided) 90%; 0.975 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Insulin Lispro A		Insulin Lispro B
Arm/Group Description	Insulin Lispro A U-200 subcutaneously (SC) once in two of four study periods. (Two doses of test [T]).		Insulin Lispro B U-100 administered SC once in two of four study periods. (Two doses of reference [R]).
All Cause Mortality
	Insulin Lispro A		Insulin Lispro B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Lispro A		Insulin Lispro B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Insulin Lispro A		Insulin Lispro B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/38 (55.3%)		16/38 (42.1%)
General disorders
Application site erythema	2/38 (5.3%)	3	1/38 (2.6%)	2
Catheter site related reaction	7/38 (18.4%)	9	5/38 (13.2%)	5
Infusion site bruising	3/38 (7.9%)	3	1/38 (2.6%)	1
Infusion site pain	5/38 (13.2%)	5	4/38 (10.5%)	4
Infusion site swelling	5/38 (13.2%)	5	4/38 (10.5%)	5
Injection site bruising	3/38 (7.9%)	3	1/38 (2.6%)	1
Pyrexia	2/38 (5.3%)	2	1/38 (2.6%)	1
Vessel puncture site bruise	1/38 (2.6%)	1	2/38 (5.3%)	2
Vessel puncture site pain	2/38 (5.3%)	2	1/38 (2.6%)	1
Injury, poisoning and procedural complications
Scratch	2/38 (5.3%)	2	0/38 (0%)	0
Nervous system disorders
Headache	2/38 (5.3%)	2	1/38 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/38 (5.3%)	2	0/38 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.