A Study of LY900014 in Participants With Type 2 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03305822
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.1
• Patients Per Site Per Month: 18.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare LY900014 with insulin lispro (Humalog) in participants with type 2 diabetes mellitus. The study will be conducted in participants with type 2 diabetes on insulin injection therapy to investigate how the body processes LY900014 and the effect of LY900014 on blood sugar levels compared to insulin lispro (Humalog).

Screening is required within 28 days prior to the start of the study. For each participant, the total duration of the clinical trial will be between 3 and 8 weeks.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: LY900014; Drug: 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: A Study to Evaluate the Pharmacokinetics and Glucodynamics of LY900014 Compared to Humalog Following a Single Dose in Patients With T2DM
• Actual Study Start Date: Oct 11, 2017
• Actual Primary Completion Date: Dec 14, 2017
• Actual Study Completion Date: Dec 14, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 Single, subcutaneous (SC) dose of 15 Units (U) LY900014 in one of two study periods	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro (Humalog) Single SC dose of 15 U insulin lispro (Humalog) in one of two study periods	Drug: Insulin Lispro; Administered SC; Other Names: LY275585 Humalog

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro Area Under the Plasma Concentration Curve Zero to 10 Hours (AUC[0-10) Following Each Treatment Arm [Predose, 5 minutes (mn), 10mn, 15mn, 20mn, 25mn, 30mn, 35mn, 40mn,45 mn,50mn, 55mn, 60mn, 70mn, 90mn, 120mn, 150mn, 180mn, 240mn, 300mn, 360mn, 420mn, 480mn, 540mn, and 600 minutes(10 hours) postdose]

   Pharmacokinetics(PK): Insulin Lispro AUC from zero to 10 hours postdose [AUC(0-10)] following each treatment arm

Secondary Outcome Measures

1. Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm [Predose, every minute starting from run-in and throughout the duration of the 10 hours]

   Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are male or female participants with Type 2 Diabetes Mellitus (T2DM) for at least 1 year

• Have a body mass index (BMI) of 18.5 to 35.0 kilogram per meter square (kg/m²)

• Have a glycated hemoglobin (HbA1c) less than (<)9.0 percent (%)

• Have had no episodes of severe hypoglycaemia in the last 6 months

Exclusion Criteria:

• Have a history or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from T2DM), hematological, or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs; of constituting a risk when taking the investigational product; or of interfering with the interpretation of data

• Have a history of renal impairment

• Have a history of deep vein thrombosis of the leg or repeated episodes of deep leg vein thrombosis in first-degree relatives

• Have proliferative retinopathy or maculopathy and/or severe neuropathy

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, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Neuss	Nordrhein-Westfalen	Germany

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)

• Study Protocol - Jul 14, 2017
• Statistical Analysis Plan - Oct 2, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03305822
• Other Study ID Numbers: 16640; I8B-MC-ITRU; 2017-001305-33
• First Posted: Oct 10, 2017
• Last Update Posted: May 27, 2020
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	LY900014/Humalog	Humalog/LY900014
Arm/Group Description	Participants receive a single, subcutaneous (SC) dose of LY900014 with a 3 day washout and a single subcutaneous (SC) 15 U dose of Humalog (insulin lispro)	Participants receive a single, subcutaneous (SC) dose of 15 U of Humalog (insulin lispro) with a 3 day washout and a single subcutaneous (SC) LY900014.
Period Title: Period 1
STARTED	20	18
Received at Least 1 Dose of Study Drug	20	18
COMPLETED	20	18
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	20	18
COMPLETED	20	18
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	20	18
Received at Least 1 Dose of Study Drug	20	18
COMPLETED	20	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	All participants received LY900014 or 15 U Humalog in a crossover design with an approximately 3 day washout period.
Overall Participants	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.0 (7.9)
Sex: Female, Male (Count of Participants)
Female	3 7.9%
Male	35 92.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	38 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	38 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Germany	38 100%
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	93.32 (13.03)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Plasma Concentration Curve Zero to 10 Hours (AUC[0-10) Following Each Treatment Arm
Description	Pharmacokinetics(PK): Insulin Lispro AUC from zero to 10 hours postdose [AUC(0-10)] following each treatment arm
Time Frame	Predose, 5 minutes (mn), 10mn, 15mn, 20mn, 25mn, 30mn, 35mn, 40mn,45 mn,50mn, 55mn, 60mn, 70mn, 90mn, 120mn, 150mn, 180mn, 240mn, 300mn, 360mn, 420mn, 480mn, 540mn, and 600 minutes(10 hours) postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and have measurable insulin lispro concentrations. No statistical analysis was done, per protocol.

Arm/Group Title	LY900014	Humalog
Arm/Group Description	Participants receive a single, subcutaneous (SC) dose of 15 U LY900014.	Participants receive a single, subcutaneous (SC) dose of 15 U of Humalog (insulin lispro).
Measure Participants	38	38
Geometric Mean (Geometric Coefficient of Variation) [hour times picomol per liter (pmol*h/L)]	1380 (22)	1280 (24)

2. Secondary Outcome

Title	Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm
Description	Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure.
Time Frame	Predose, every minute starting from run-in and throughout the duration of the 10 hours

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	LY900014	Humalog
Arm/Group Description	Participants receive a single, subcutaneous (SC) dose of 15 U LY900014.	Participants receive a single, subcutaneous (SC) dose of 15 U of Humalog (insulin lispro).
Measure Participants	37	38
Geometric Mean (Geometric Coefficient of Variation) [milligram/kilogram (mg/kg)]	749 (59)	647 (70)

Adverse Events

Time Frame	Baseline until the end of study (60 days)
Arm/Group Title	15 U LY900014		Humalog
Arm/Group Description	Participants received a single, subcutaneous (SC) dose 15U LY900014.		Participants received a single, subcutaneous (SC) dose 15 U of Humalog (insulin lispro).
All Cause Mortality
	15 U LY900014		Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/38 (0%)
Serious Adverse Events
	15 U LY900014		Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		1/38 (2.6%)
Cardiac disorders
Coronary artery stenosis	0/38 (0%)	0	1/38 (2.6%)	1
Other (Not Including Serious) Adverse Events
	15 U LY900014		Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/38 (10.5%)		2/38 (5.3%)
General disorders
Vessel puncture site thrombosis	2/38 (5.3%)	2	0/38 (0%)	0
Nervous system disorders
Headache	2/38 (5.3%)	2	2/38 (5.3%)	2

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.