A Study of LY900014 in Elderly and Younger Adult Participants With Type 1 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03166124
• Collaborator: (none)
• Enrollment: 80
• Locations: 2
• Arms: 4
• Actual Duration (Months): 5.8
• Patients Per Site: 40
• Patients Per Site Per Month: 6.8

Study Details

Study Description

Brief Summary

The purpose of this study is to compare LY900014 with insulin lispro (Humalog) in elderly and younger adults with type 1 diabetes mellitus.

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 to 8 weeks.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: LY900014; Drug: Insulin Lispro	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Pharmacokinetics and Glucodynamics of LY900014 Compared to Insulin Lispro Following Single Dose Administration in Elderly and Younger Adults With Type 1 Diabetes Mellitus
• Actual Study Start Date: May 24, 2017
• Actual Primary Completion Date: Nov 18, 2017
• Actual Study Completion Date: Nov 18, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elderly Adults LY900014 Single, subcutaneous (SC) 15-U dose of LY900014 in the elderly adult group.	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Active Comparator: Elderly Adults Insulin Lispro Single, SC 15-U dose of insulin lispro (Humalog) in in the elderly adult group.	Drug: Insulin Lispro; Administered SC; Other Names: Humalog LY275585
Experimental: Younger Adults LY900014 Single, SC 15-U dose of LY900014 in the younger adult group.	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Active Comparator: Younger Adults Insulin Lispro Single, SC 15-U dose of insulin lispro (Humalog) in the younger adult group.	Drug: Insulin Lispro; Administered SC; Other Names: Humalog LY275585

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) for Each Treatment Arm [Day 1: Pre-dose, 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 post-dose]

   Pharmacokinetics: Insulin lispro AUC from time zero to 10 hours postdose [AUC(0-10h)] for each treatment arm.

Secondary Outcome Measures

1. Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm [Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose]

   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 and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are male or female participants with Type 1 Diabetes Mellitus (T1DM)

• Have a body mass index (BMI) of 18.5 to 30.0 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 T1DM), 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.	Mainz		Germany
2	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		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 - Aug 4, 2017
• Statistical Analysis Plan - Sep 11, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03166124
• Other Study ID Numbers: 16637; I8B-MC-ITRR
• First Posted: May 24, 2017
• Last Update Posted: Apr 30, 2020
• Last Verified: Dec 1, 2017

• 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 1; Insulin Lispro

Study Results

Participant Flow

Pre-assignment Detail	This is a 2-period, crossover study, up to 10-hour euglycemic clamp in which participants were randomized to 1 of 2 treatment sequences: LY900014 in Period 1 switching to Humalog period 2 or Humalog in Period 1 switching to LY900014 in Period 2. A washout period of 3 to 15 days occurred between study drug administration.

Arm/Group Title	Sequence 1 AB Elderly Adults	Sequence 1 AB Younger Adults	Sequence 2 BA Elderly Adults	Sequence 2 BA Younger Adults
Arm/Group Description	Sequence 1: A: Single, subcutaneous (SC) 15-U dose of LY900014 in Period 1. B: Single, SC 15-U dose of Humalog in Period 2. Washout period of 3-15 days between study drug administration.	Sequence 1 A: Single, SC 15-U dose of LY900014 in Period 1. B: single, SC 15-U dose of Humalog in Period 2. Washout 3-15 days between study drug administration.	Sequence 2: B: Single, SC 15-U dose of Humalog in Period 1. A: Single, SC 15-U dose of LY900014 in Period 2. A Washout period of 3-15 days between study drug administration.	Sequence 2: B: Single, SC 15-U dose of Humalog in Period 1. A: Single SC 15-U dose of LY900014 in Period 2. A Washout period of 3-15 days between study drug administration.
Period Title: Treatment Period 1
STARTED	20	20	19	21
Received at Least One Dose of Study Drug	20	20	18	21
COMPLETED	20	20	18	21
NOT COMPLETED	0	0	1	0
Period Title: Treatment Period 1
STARTED	20	20	18	21
COMPLETED	20	18	17	20
NOT COMPLETED	0	2	1	1
Period Title: Treatment Period 1
STARTED	20	18	17	20
COMPLETED	20	18	17	20
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Elderly Adults	Younger Adults	Total
Arm/Group Description	Male and female participants age 65 or older inclusive.	Male and female participants age 18 to 45 inclusive.	Total of all reporting groups
Overall Participants	39	41	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.5 (2.7)	32.0 (6.8)	49.8 (19.1)
Sex: Female, Male (Count of Participants)
Female	17 43.6%	13 31.7%	30 37.5%
Male	22 56.4%	28 68.3%	50 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	39 100%	41 100%	80 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	39 100%	41 100%	80 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Germany	39 100%	41 100%	80 100%
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	76.66 (12.61)	78.39 (10.00)	77.55 (11.41)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) for Each Treatment Arm
Description	Pharmacokinetics: Insulin lispro AUC from time zero to 10 hours postdose [AUC(0-10h)] for each treatment arm.
Time Frame	Day 1: Pre-dose, 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 post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and have measurable insulin lispro concentrations.

Arm/Group Title	Elderly Adults LY900014	Elderly Adults Humalog	Younger Adults LY900014	Younger Adults Humalog
Arm/Group Description	All elderly adults who received a single 15-U SC dose LY900014.	All elderly adults who received a single 15-U SC dose Humalog.	All younger adults who received a single 15-U SC dose LY900014.	All younger adults who received single 15-U SC dose Humalog.
Measure Participants	37	37	40	39
Geometric Mean (Geometric Coefficient of Variation) [picomole * hour per Liter (pmol*h/L)]	1430 (26)	1400 (29)	1210 (24)	1170 (30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elderly Adults LY900014, Elderly Adults Humalog
	Comments	Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.953 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Younger Adults LY900014, Younger Adults Humalog
	Comments	Geometric Least Squares Means (LSMeans) were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.974 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	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	Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and completed at least one clamp procedure.

Arm/Group Title	Elderly Adults LY900014	Elderly Adults Humalog	Younger Adults LY900014	Younger Adults Humalog
Arm/Group Description	All elderly adults who received a single 15-U SC dose LY900014.	All elderly adults who received a single 15-U SC dose Humalog.	All younger adults who received a single 15-U SC dose LY900014.	All younger adults who received a single 15-U SC dose Humalog.
Measure Participants	37	35	40	39
Geometric Mean (Geometric Coefficient of Variation) [milligram per kilogram (mg/kg)]	1140 (42)	1090 (43)	1170 (33)	1150 (30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elderly Adults LY900014, Elderly Adults Humalog
	Comments	Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Younger Adults LY900014, Younger Adults Humalog
	Comments	Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Baseline to end of study (up to 39 days)
Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	Elderly Adults LY900014		Elderly Adults Humalog		Younger Adults LY900014		Younger Adults Humalog
Arm/Group Description	Single, subcutaneous (SC) 15-U dose of LY900014.		Single, SC 15-U dose of Humalog.		Single, SC 15-U dose of LY900014.		Single, SC 15-U dose of Humalog.
All Cause Mortality
	Elderly Adults LY900014		Elderly Adults Humalog		Younger Adults LY900014		Younger Adults Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/38 (0%)		0/40 (0%)		0/39 (0%)
Serious Adverse Events
	Elderly Adults LY900014		Elderly Adults Humalog		Younger Adults LY900014		Younger Adults Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/38 (0%)		1/40 (2.5%)		0/39 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/37 (0%)	0	0/38 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Other (Not Including Serious) Adverse Events
	Elderly Adults LY900014		Elderly Adults Humalog		Younger Adults LY900014		Younger Adults Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/37 (13.5%)		7/38 (18.4%)		3/40 (7.5%)		6/39 (15.4%)
Gastrointestinal disorders
Nausea	1/37 (2.7%)	1	2/38 (5.3%)	2	2/40 (5%)	2	4/39 (10.3%)	4
Vomiting	3/37 (8.1%)	4	5/38 (13.2%)	5	3/40 (7.5%)	3	4/39 (10.3%)	4
Infections and infestations
Nasopharyngitis	2/37 (5.4%)	2	0/38 (0%)	0	1/40 (2.5%)	1	1/39 (2.6%)	1
Nervous system disorders
Headache	1/37 (2.7%)	1	4/38 (10.5%)	4	2/40 (5%)	2	3/39 (7.7%)	3

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.