A Study of LY900014 Formulations in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02317575
• Collaborator: (none)
• Enrollment: 29
• Location: 1
• Arms: 6
• Duration (Months): 8
• Patients Per Site Per Month: 3.6

Study Details

Study Description

Brief Summary

This study evaluated four test formulations of a glucose lowering drug (LY900014) administered by injection under the skin of the abdomen. The study was conducted in healthy people to investigate how the human body handles LY900014 and the effect of LY900014 on blood sugar levels. Side effects and tolerability were documented. The study was to be conducted in two parts (Part A and Part B) to achieve its objectives. Each part of the study was to last for about 11 to 12 weeks, including screening and follow up. Screening was required within 28 days prior to entering into either study Part A or Part B. Part B was not executed because no suitable formulation was identified.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Biological: LY900014; Biological: Insulin Lispro	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Safety, Tolerability, Pharmacokinetics and Glucodynamics of Multiple Insulin Lispro (LY900014) Formulations
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: LY900014 Test A Test Formulation A. Single dose of LY900014 administered subcutaneously (SC) in one of five periods.	Biological: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Experimental: Part A:Insulin Lispro Reference formulation. 15 U insulin lispro administered SC in one of five periods.	Biological: Insulin Lispro; Administered SC; Other Names: LY275585
Experimental: Part A: LY900014 Test B Test Formulation B. Single dose LY900014 administered subcutaneously (SC) in one of five periods.	Biological: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Experimental: Part A: LY900014 Test C Test Formulation C. Single dose LY900014administered subcutaneously (SC) in one of five periods.	Biological: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Experimental: Part A: LY900014 Test D Test Formulation D. Single dose LY900014administered subcutaneously (SC) in one of five periods.	Biological: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Experimental: Part B: LY900014 Test formulation selected from Part A. Single dose of LY900014 administered SC in one of four periods.	Biological: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro

Outcome Measures

Primary Outcome Measures

1. Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) [30 minutes predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose]

Secondary Outcome Measures

1. Part A: Visual Analog Scale (VAS) Score for Injection Site Pain [Predose, 1, 20, 60 minutes postdose and at the end of the clamp procedure]

   The Visual Analog Scale (VAS) assessed injection site pain on a scale of 0-100 millimeter (mm) range (0 = no pain and 100 worst imaginable pain).

2. Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp [Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes postdose]

   Gtot is the total glucose infusion over the clamp duration and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure.

3. Part B: Total Amount of Glucose Infused (Gtot) Over the Duration of the Clamp - Interparticipant Variability [Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes, then every 20 minutes from 300 to 480 minutes postdose]

   Gtot is the total glucose infusion over the clamp duration and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure.

4. Part B: Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) - Interparticipant Variability [Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Overtly healthy male or a female (not pregnant and agreeable to take birth control measures until one month after study completion)

• Have a body mass index (BMI) of 18.5 to 30 kilogram per square meter (kg/m^2), inclusive, at screening

• Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results that are acceptable for the study

• Are nonsmokers, have not smoked for at least 2 months prior to entering the study, and agree not to smoke (cigars, cigarettes, or pipes) or use smokeless tobacco for the duration of the study

Exclusion Criteria:

• Are currently participating in or completed a clinical trial within the last 30 days from a clinical trial or any other type of medical research judged to be incompatible with this study

• Have previously participated or withdrawn from this study

• Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study

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: NCT02317575
• Other Study ID Numbers: 15645; I8B-FW-ITRA
• First Posted: Dec 16, 2014
• Last Update Posted: May 13, 2020
• Last Verified: Sep 1, 2015

• Additional relevant MeSH terms: Insulin Lispro

Study Results

Participant Flow

Recruitment Details	Part B was not executed and no data were collected.
Pre-assignment Detail	Part A was a 5-period crossover study of four LY900014 formulations (Tests A, B, C, and D) and insulin lispro (Reference (R)). A minimum of 3 days washout between each period.

Arm/Group Title	Part A Sequence 1, CDABR	Part A Sequence 2, ABDRC	Part A Sequence 3, BCRAD	Part A Sequence 4, DRBCA	Part A Sequence 5, RACDB
Arm/Group Description	Period 1: LY900014 Test C, Period 2: LY900014 Test D, Period 3: LY900014 Test A, Period 4: LY900014 Test B, Period 5: Reference (R) = insulin lispro	Period 1: LY900014 Test A, Period 2: LY900014 Test B, Period 3: LY900014 Test D, Period 4: Reference (R) = insulin lispro, Period 5: LY900014 Test C	Period 1: LY900014 Test B, Period 2: LY900014 Test C, Period 3: Reference (R) = insulin lispro, Period 4: LY900014 Test A, Period 5: LY900014 Test D	Period 1: LY900014 Test D, Period 2: Reference (R) = insulin lispro, Period 3: LY900014 Test B, Period 4: LY900014 Test C, Period 5: LY900014 Test A	Period 1: Reference (R) = insulin lispro, Period 2: LY900014 Test A, Period 3: LY900014 Test C, Period 4: LY900014 Test D, Period 5: LY900014 Test B
Period Title: Period 1
STARTED	5	6	6	6	6
Received at Least 1 Dose of Study Drug	5	5	6	6	6
COMPLETED	4	5	6	6	6
NOT COMPLETED	1	1	0	0	0
Period Title: Period 1
STARTED	4	5	6	6	6
COMPLETED	4	5	6	6	6
NOT COMPLETED	0	0	0	0	0
Period Title: Period 1
STARTED	4	5	6	6	6
COMPLETED	4	5	6	6	6
NOT COMPLETED	0	0	0	0	0
Period Title: Period 1
STARTED	4	5	6	6	6
COMPLETED	4	5	6	6	6
NOT COMPLETED	0	0	0	0	0
Period Title: Period 1
STARTED	4	5	6	6	6
COMPLETED	4	5	6	6	6
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Participants were administered LY900014 SC Tests A, B, C, and D, with that of 15 U of insulin lispro alone (Reference) in healthy subjects.
Overall Participants	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.5 (10.8)
Sex: Female, Male (Count of Participants)
Female	27 96.4%
Male	1 3.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	28 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	27 96.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 3.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Singapore	28 100%
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	72.60 (9.07)
Body Mass Index (BMI) (kilogram per meter squared (kg/m²)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per meter squared (kg/m²)]	24.43 (2.21)

Outcome Measures

1. Primary Outcome

Title	Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast)
Time Frame	30 minutes predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and completed the dose sequence.

Arm/Group Title	Part A: Formulation A, LY900014	Part A: Formulation B, LY900014	Part A: Formulation C, LY900014	Part A: Formulation D, LY900014	Part A: Reference
Arm/Group Description	Single dose LY900014 administered subcutaneously (SC) in one of five periods	Single dose LY900014 administered subcutaneously (SC) in one of five periods	Single dose LY900014 administered subcutaneously (SC) in one of five periods	Single dose LY900014 administered subcutaneously (SC) in one of five periods	15 U of insulin lispro administered subcutaneously (SC) in one of five periods
Measure Participants	27	27	28	27	27
Geometric Least Squares Mean (Geometric Coefficient of Variation) [picomol times hour per liter (pmol*h/L)]	1720 (20)	1740 (17)	1810 (21)	1750 (19)	1690 (19)

2. Secondary Outcome

Title	Part A: Visual Analog Scale (VAS) Score for Injection Site Pain
Description	The Visual Analog Scale (VAS) assessed injection site pain on a scale of 0-100 millimeter (mm) range (0 = no pain and 100 worst imaginable pain).
Time Frame	Predose, 1, 20, 60 minutes postdose and at the end of the clamp procedure

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug.

Arm/Group Title	Part A: Formulation A, LY900014	Part A: Formulation B, LY900014	Part A: Formulation C, LY900014	Part A: Formulation D, LY900014	Part A: Reference
Arm/Group Description	15 U LY900014 administered SC in one of five periods	15 U LY900014 administered SC in one of five periods	115 U LY900014 administered SC in one of five periods	15 U LY900014 administered SC in one of five periods	15 U of insulin lispro administered subcutaneously (SC) in one of five periods
Measure Participants	27	27	28	27	27
1 minute	0.1 (0.6)	2.1 (6.5)	1.8 (4.8)	1.3 (4.7)	0.5 (1.9)
20 minutes	0 (0)	0 (0)	0 (0)	2.0 (9.6)	0 (0)
60 minutes	0 (0)	0 (0)	0 (0)	1.1 (6.0)	0 (0)
End of clamp	0 (0)	0 (0)	0 (0)	0 (0.2)	0 (0)

3. Secondary Outcome

Title	Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp
Description	Gtot is the total glucose infusion over the clamp duration and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure.
Time Frame	Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and completed the dose sequence.

Arm/Group Title	Part A: Formulation A, LY900014	Part A: Formulation B, LY900014	Part A: Formulation C, LY900014	Part A: Formulation D, LY900014	Part A: Reference
Arm/Group Description	15 U LY900014 administered SC in one of five periods	15 U LY900014 administered SC in one of five periods	15 U LY900014 administered SC in one of five periods	15 U LY900014 administered SC in one of five periods	15 U of insulin lispro administered subcutaneously (SC) in one of five periods
Measure Participants	27	27	28	27	27
Geometric Least Squares Mean (Geometric Coefficient of Variation) [milligram (mg)]	78372 (29)	81776 (41)	82365 (35)	80186 (34)	75571 (37)

4. Secondary Outcome

Title	Part B: Total Amount of Glucose Infused (Gtot) Over the Duration of the Clamp - Interparticipant Variability
Description	Gtot is the total glucose infusion over the clamp duration and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure.
Time Frame	Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes, then every 20 minutes from 300 to 480 minutes postdose

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed as Part B was not executed.

Arm/Group Title	Part B:LY900014
Arm/Group Description	Formulation selected from Part A. Single dose of LY900014 administered SC in one of four periods.
Measure Participants	0

5. Secondary Outcome

Title	Part B: Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) - Interparticipant Variability
Time Frame	Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed as Part B was not executed.

Arm/Group Title	Part B:LY900014
Arm/Group Description	Formulation selected from Part A. Single dose of LY900014 administered SC in one of four periods.
Measure Participants	0

Adverse Events

Arm/Group Title	Part A: Formulation A, LY900014		Part A: Formulation B, LY900014		Part A: Forumulation C, LY900014		Part A: Forumulation D, LY900014		Part A: Reference
Arm/Group Description	Single dose LY900014 administered subcutaneously (SC) in one of five periods		Single dose LY900014 administered subcutaneously (SC) in one of five periods		Single dose LY900014 administered subcutaneously (SC) in one of five periods		Single dose LY900014 administered subcutaneously (SC) in one of five periods		15 U insulin lispro administered subcutaneously (SC)
All Cause Mortality
	Part A: Formulation A, LY900014		Part A: Formulation B, LY900014		Part A: Forumulation C, LY900014		Part A: Forumulation D, LY900014		Part A: Reference
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: Formulation A, LY900014		Part A: Formulation B, LY900014		Part A: Forumulation C, LY900014		Part A: Forumulation D, LY900014		Part A: Reference
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)		0/28 (0%)		0/27 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Formulation A, LY900014		Part A: Formulation B, LY900014		Part A: Forumulation C, LY900014		Part A: Forumulation D, LY900014		Part A: Reference
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/27 (18.5%)		5/27 (18.5%)		2/28 (7.1%)		6/27 (22.2%)		2/27 (7.4%)
General disorders
Catheter site related reaction	5/27 (18.5%)	5	5/27 (18.5%)	5	2/28 (7.1%)	2	6/27 (22.2%)	6	2/27 (7.4%)	2

Limitations/Caveats

Part B was not executed per protocol because no formulation was identified in Part A.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.