A Study of LY900014 in Healthy Chinese Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04049123
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Actual Duration (Months): 11.2
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate a new formulation of insulin lispro, LY900014, which is a drug that lowers blood sugar. The study will look at how the body processes LY900014 and the effect of LY900014 on blood sugar levels. For each participant, the study will consist of 3 periods and will last about 51 days.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: A Study to Evaluate the Pharmacokinetics and Glucodynamics of LY900014 Following Single Dose Administration in Healthy Chinese Subjects
• Actual Study Start Date: Nov 18, 2019
• Actual Primary Completion Date: Oct 23, 2020
• Actual Study Completion Date: Oct 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Insulin Lispro (Humalog) 15 units (U) Insulin Lispro (Humalog) administered once, subcutaneously (SC), in one of three study periods.	Drug: Insulin Lispro; Administered SC; Other Names: LY275585 Humalog
Experimental: LY900014 7 U, and 15 U LY900014 administered once, SC, in two of three study periods.	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro Area Under the Serum Concentration Versus Time Curve From Time Zero to 10 Hours Postdose (AUC[0-10h]) [Day 1: Predose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, 420, 480, 540, and 600 minutes postdose]

   PK: Insulin Lispro AUC(0-10h)

Secondary Outcome Measures

1. Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot) [Day 1: Predose: -10, -20, -30 minutes; During clamp: every 2.5 to 3 minutes for the first 30 minutes; every 5 minutes for 30 to 120 minutes; every 10 minutes for 120 to 480 minutes and every 20 minutes for 480 to 600 minutes postdose]

   Gtot is the total amount of glucose infused over the duration of the clamp procedure (10 hours) for each study period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Are overtly healthy native Chinese males or females

• Female participants:

• Women of child-bearing potential who are abstinent or use effective methods of contraception for the entirety of the study.

• Women not of child-bearing potential who are infertile or post-menopausal

• Have a body mass index (BMI) of 18 to 28 kilograms per square meter (kg/m²)

• Are nonsmokers

• Have a fasting plasma glucose value >71 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]) and <108 mg/dL (6.0 mmol/L)

Exclusion Criteria:

• Are currently enrolled in a clinical study, or have participated, within the last 30 days, in a clinical study involving an investigational product

• Have previously completed or withdrawn from this study or any other study investigating LY900014

• Have known allergies to LY900014 or any components of the formulation

• Have a significant history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, 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

• Intend to use over-the-counter or prescription medication within 7 and 14 days, respectively, prior to dosing or during the study.

• Have donated blood of more than 400 milliliters (mL) within the previous 6 months of study screening or donated more than 100 mL within the last 30 days.

• Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West China Hospital Sichuan University	Cheng Du	Cn-51	China	610041

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 - Feb 20, 2019
• Statistical Analysis Plan - Nov 1, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04049123
• Other Study ID Numbers: 16644; I8B-MC-ITRY
• First Posted: Aug 7, 2019
• Last Update Posted: Nov 16, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Insulin Lispro

Study Results

Participant Flow

Pre-assignment Detail	This was a 3-period crossover study in which participants received a single 7 Unit (U), and a single 15 U subcutaneous (SC) dose of LY900014 in two of three dosing sequences, and 15 U SC dose of Humalog in one of three dosing sequences. There was a washout period of ≥ 3 days between euglycemic clamp visits.

Arm/Group Title	Sequence 1: CAB	Sequence 2: ACB	Sequence 3: ABC
Arm/Group Description	Participants received a single SC dose in each treatment period. C = 15 U Humalog A = 7 U LY900014 B = 15 U LY900014	Participants received a single SC dose in each treatment period. A = 7 U LY900014 C = 15 U Humalog B = 15 U LY900014	Participants received a single SC dose in each treatment period. A = 7 U LY900014 B = 15 U LY900014 C = 15 U Humalog
Period Title: Period 1
STARTED	5	5	5
Received at Least One Dose of Study Drug	5	5	5
COMPLETED	5	5	5
NOT COMPLETED	0	0	0
Period Title: Period 1
STARTED	5	5	5
COMPLETED	5	5	5
NOT COMPLETED	0	0	0
Period Title: Period 1
STARTED	5	5	5
COMPLETED	5	5	5
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Baseline
Arm/Group Description	Participants received a single 7 U, and a single 15 U SC dose of LY900014 in 2 of 3 periods and 15 U SC dose of Humalog in 1 of 3 periods.
Overall Participants	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.0 (3.7)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	15 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	15 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	15 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
China	15 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Area Under the Serum Concentration Versus Time Curve From Time Zero to 10 Hours Postdose (AUC[0-10h])
Description	PK: Insulin Lispro AUC(0-10h)
Time Frame	Day 1: Predose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, 420, 480, 540, and 600 minutes postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and have evaluable PK data.

Arm/Group Title	7 U LY900014	15 U LY900014	15 U Humalog
Arm/Group Description	Single SC dose 7 U LY900014.	Single SC dose 15 U LY900014.	Single SC dose 15 U Humalog.
Measure Participants	15	15	15
Geometric Mean (Geometric Coefficient of Variation) [picomole * hour per Liter (pmol*h/L)]	708 (12)	1580 (11)	1600 (12)

2. Secondary Outcome

Title	Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot)
Description	Gtot is the total amount of glucose infused over the duration of the clamp procedure (10 hours) for each study period.
Time Frame	Day 1: Predose: -10, -20, -30 minutes; During clamp: every 2.5 to 3 minutes for the first 30 minutes; every 5 minutes for 30 to 120 minutes; every 10 minutes for 120 to 480 minutes and every 20 minutes for 480 to 600 minutes postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable glucodynamic (GD) data.

Arm/Group Title	7 U LY900014	15 U LY900014	15 U Humalog
Arm/Group Description	Single SC dose 7 U LY900014.	Single SC dose 15 U LY900014.	Single SC dose 15 U Humalog.
Measure Participants	15	15	15
Geometric Mean (Geometric Coefficient of Variation) [milligram per kilogram (mg/kg)]	989 (35)	1540 (40)	1720 (32)

Adverse Events

Time Frame	Baseline to end of study (up to 183 days).
Adverse Event Reporting Description	All enrolled participants, whether or not they completed all protocol requirements.
Arm/Group Title	7 Unit (U) LY900014		15 U LY900014		15 U Humalog
Arm/Group Description	Single subcutaneous (SC) dose 7 U LY900014.		Single SC dose 15 U LY900014.		Single SC dose 15 U Humalog.
All Cause Mortality
	7 Unit (U) LY900014		15 U LY900014		15 U Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)		0/15 (0%)
Serious Adverse Events
	7 Unit (U) LY900014		15 U LY900014		15 U Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	7 Unit (U) LY900014		15 U LY900014		15 U Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)		4/15 (26.7%)		0/15 (0%)
Cardiac disorders
Nodal rhythm	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Hepatobiliary disorders
Hepatic function abnormal	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Investigations
Alanine aminotransferase increased	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Blood creatine phosphokinase increased	0/15 (0%)	0	3/15 (20%)	3	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.