Bioequivalence of Two Lispro Formulations

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01133392
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 13.6

Study Details

Study Description

Brief Summary

This study will compare how the body treats 2 different forms of insulin lispro and how they affect blood sugar levels.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Insulin lispro A; Drug: Insulin lispro B	Phase 1

Detailed Description

The 2 formulations of insulin lispro will be referred to here as:

Lispro A

Lispro B

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Bioequivalence of Two Formulations of Insulin Lispro in Healthy Subjects
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin Lispro A 20 units (U) subcutaneously (SC)	Drug: Insulin lispro A; 20 units (U) subcutaneously (SC).; Other Names: LY275585
Active Comparator: Insulin lispro B 20 units (U) subcutaneously (SC)	Drug: Insulin lispro B; 20 U subcutaneously (SC).; Other Names: LY275585

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC0-tlast] [0 up to 8 hours post dose]

   Primary outcome measure is based on the pharmacokinetic area under the concentration-time curve from time 0 to the last time point with a measurable concentration.

Secondary Outcome Measures

1. Pharmacokinetic Parameter: Maximum Serum Insulin Concentration [Cmax] [0 to 8 hours post dose]

   The maximum observed insulin lispro concentration following dosing.

2. Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax) [0 to 8 hours post dose]

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

3. Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax) [0 to 8 hours post dose]

   Time of maximal glucose infusion rate.

4. Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot) [0 to 8 hours post dose]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 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 kilograms 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 (FBG, plasma) >6 millimoles/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

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: NCT01133392
• Other Study ID Numbers: 13300; F3Z-EW-IOPY
• First Posted: May 28, 2010
• Last Update Posted: Dec 30, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by Eli Lilly and Company: insulin; lispro
• Additional relevant MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Lispro

Study Results

Participant Flow

Pre-assignment Detail	41 participants were enrolled into the study. 3 participants discontinued due to subject decision prior to receiving treatment.

Arm/Group Title	Insulin Lispro Dosing Sequence ABAB	Insulin Lispro Dosing Sequence BABA
Arm/Group Description	Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence ABAB. There was an interval of approximately 4 to 7 days between doses.	Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence BABA. There was an interval of approximately 4 to 7 days between doses.
Period Title: First Intervention (1 Day )
STARTED	20	18
COMPLETED	20	18
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day )
STARTED	20	18
COMPLETED	20	17
NOT COMPLETED	0	1
Period Title: First Intervention (1 Day )
STARTED	20	17
COMPLETED	20	17
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day )
STARTED	20	17
COMPLETED	20	17
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day )
STARTED	20	17
COMPLETED	20	17
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day )
STARTED	20	17
COMPLETED	20	16
NOT COMPLETED	0	1
Period Title: First Intervention (1 Day )
STARTED	20	16
COMPLETED	20	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Insulin Lispro Dosing Sequence ABAB	Insulin Lispro Dosing Sequence BABA	Total
Arm/Group Description	Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence ABAB.	Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence BABA.	Total of all reporting groups
Overall Participants	20	18	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.4 (7.2)	34.6 (6.4)	32.4 (7.1)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 11.1%	2 5.3%
Male	20 100%	16 88.9%	36 94.7%
Race/Ethnicity, Customized (participants) [Number]
Not Hispanic or Latino	20 100%	18 100%	38 100%
Hispanic or Latino	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Singapore	20 100%	18 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC0-tlast]
Description	Primary outcome measure is based on the pharmacokinetic area under the concentration-time curve from time 0 to the last time point with a measurable concentration.
Time Frame	0 up to 8 hours post dose

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	20 units (U) administered subcutaneously (SC)	20 units (U) administered subcutaneously (SC)
Measure Participants	37	38
Geometric Mean (Geometric Coefficient of Variation) [picomole*hour/liter (pmol*h/L)]	1920 (20)	1940 (20)

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	0.990
	Confidence Interval	(2-Sided) 90%; 0.948 to 1.034
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Pharmacokinetic Parameter: Maximum Serum Insulin Concentration [Cmax]
Description	The maximum observed insulin lispro concentration following dosing.
Time Frame	0 to 8 hours post dose

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	20 units (U) administered subcutaneously (SC)	20 units (U) administered subcutaneously (SC)
Measure Participants	37	38
Geometric Mean (Geometric Coefficient of Variation) [picomole/liter (pmol/L)]	819 (32)	887 (34)

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	0.933
	Confidence Interval	(2-Sided) 90%; 0.897 to 0.972
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax)
Description	The maximum observed glucose infusion rate during the euglycemic clamp procedure.
Time Frame	0 to 8 hours post dose

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	20 units (U) administered subcutaneously (SC)	20 units (U) administered subcutaneously (SC)
Measure Participants	37	38
Geometric Mean (Geometric Coefficient of Variation) [milligrams per minute (mg/min)]	544 (23)	539 (27)

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	1.005
	Confidence Interval	(2-Sided) 90%; 0.958 to 1.054
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax)
Description	Time of maximal glucose infusion rate.
Time Frame	0 to 8 hours post dose

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	20 units (U) administered subcutaneously (SC)	20 units (U) administered subcutaneously (SC)
Measure Participants	37	38
Geometric Mean (Geometric Coefficient of Variation) [hours]	2.11 (49)	2.00 (56)

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	0.100
	Confidence Interval	(2-Sided) 90%; -0.400 to 0.500
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. 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	0 to 8 hours post dose

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	20 units (U) administered subcutaneously (SC)	20 units (U) administered subcutaneously (SC)
Measure Participants	37	38
Geometric Mean (Geometric Coefficient of Variation) [grams (g)]	125 (25)	123 (30)

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	1.014
	Confidence Interval	(2-Sided) 90%; 0.961 to 1.070
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Arm/Group Title	Insulin Lispro A		Insulin Lispro B
Arm/Group Description	Insulin lispro A formulation (Treatment A, test - 2 occasions)		Insulin lispro B formulation (Treatment B, reference - 2 occasions)
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	0/37 (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	9/37 (24.3%)		12/38 (31.6%)
Eye disorders
Eye discharge	0/37 (0%)	0	1/38 (2.6%)	1
Gastrointestinal disorders
Diarrhoea	0/37 (0%)	0	1/38 (2.6%)	1
General disorders
Catheter site haematoma	5/37 (13.5%)	5	4/38 (10.5%)	6
Catheter site pain	1/37 (2.7%)	1	1/38 (2.6%)	1
Catheter site swelling	0/37 (0%)	0	2/38 (5.3%)	2
Injection site pain	2/37 (5.4%)	2	0/38 (0%)	0
Injection site swelling	1/37 (2.7%)	1	0/38 (0%)	0
Injury, poisoning and procedural complications
Contusion	1/37 (2.7%)	1	0/38 (0%)	0
Excoriation	1/37 (2.7%)	1	0/38 (0%)	0
Fall	1/37 (2.7%)	1	0/38 (0%)	0
Head injury	0/37 (0%)	0	1/38 (2.6%)	1
Procedural site reaction	1/37 (2.7%)	3	1/38 (2.6%)	2
Thermal burn	0/37 (0%)	0	1/38 (2.6%)	1
Investigations
Blood urine present	1/37 (2.7%)	1	0/38 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/37 (2.7%)	1	0/38 (0%)	0
Joint swelling	1/37 (2.7%)	1	0/38 (0%)	0
Myalgia	1/37 (2.7%)	1	1/38 (2.6%)	1
Nervous system disorders
Dizziness	1/37 (2.7%)	1	0/38 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/37 (0%)	0	1/38 (2.6%)	1
Oropharyngeal pain	0/37 (0%)	0	2/38 (5.3%)	2
Rhinorrhoea	0/37 (0%)	0	1/38 (2.6%)	1
Vascular disorders
Flushing	0/37 (0%)	0	1/38 (2.6%)	1

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.