A Meal Test Study of LY900014 in Participants With Type 1 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03449433
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 5
• Actual Duration (Months): 5
• Patients Per Site Per Month: 16

Study Details

Study Description

Brief Summary

Two forms of insulin lispro (LY900014 and Humalog®) and two forms of insulin aspart (NovoRapid® and Fiasp®) will be given to trial participants with diabetes mellitus type 1 by injection under the skin. The study will assess how fast the active ingredient (insulin lispro or insulin aspart) gets into the blood stream and how long it takes the body to remove it. A test meal will be given to trial participants to assess the course of the blood sugar lowering effect of the investigational products. The safety and tolerability of LY900014 will also be assessed. Screening is required within 14 days prior to the lead in. For each participant, the study will last up to 91 days.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: LY900014; Drug: Insulin Lispro; Drug: Insulin Aspart; Drug: Insulin Aspart	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: A Mixed Meal Tolerance Test Study to Evaluate the Pharmacokinetics and Pharmacodynamics of LY900014 Compared to Humalog Following a Single Dose in Adults With Type 1 Diabetes
• Actual Study Start Date: Mar 15, 2018
• Actual Primary Completion Date: Aug 14, 2018
• Actual Study Completion Date: Aug 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY900014 T1DM participants received a single, individualized, subcutaneous (SC) dose of LY900014.	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro (Humalog®) T1DM participants received a single, individualized, SC dose of insulin lispro.	Drug: Insulin Lispro; Administered SC; Other Names: Humalog® LY275585
Active Comparator: Insulin Aspart (NovoRapid®) T1DM participants received a single, individualized, SC dose of insulin aspart.	Drug: Insulin Aspart; Administered SC; Other Names: NovoRapid®
Active Comparator: Insulin Aspart (Fiasp®) T1DM participants received a single, individualized, SC dose of insulin aspart.	Drug: Insulin Aspart; Administered SC; Other Names: Fiasp®
No Intervention: Healthy Participants Healthy participants who received no study drug.

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Insulin Lispro or Insulin Aspart Area Under the Concentration Curve From Zero to Seven Hours (AUC 0-7h) Following Administration of Each Study Arm [0 (predose), 1, 2, 3,5,10, 15, 20, 25, 30,35, 40, 45, 50, 55,60, 70, 90, 120, 150,180, 240, 300, 360 and 420 minutes postdose]

   PK: Insulin Lispro or Insulin Aspart AUC(0-7h)

Secondary Outcome Measures

1. Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) [Time Frame:-30, -15, 0 (predose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, and 300 minutes postdose]

   PD: AUC(0-5h) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Profil Institut für Stoffwechselforschung	Neuss	Nordrhein-Westfalen	Germany	41460

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 - Apr 10, 2018
• Statistical Analysis Plan - Mar 8, 2018

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03449433
• Other Study ID Numbers: 16911; I8B-MC-ITSL; 2017-003459-47
• First Posted: Feb 28, 2018
• Last Update Posted: Apr 30, 2020
• Last Verified: Sep 1, 2018

• 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: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	Type 1 Diabetes Mellitus (T1DM) Cohort 1	T1DM Cohort 2	T1DM Cohort 3	T1DM Cohort 4	Healthy Participants
Arm/Group Description	Period 1: LY900014 administered subcutaneously (SC) immediately before meal Period 2: insulin n Aspart (Fiasp®) administered SC Period 3:Insulin Lispro (Humalog®) administered SC Period 4: Insulin Aspart (NovoRapid®) administered SC with 21 hours between doses	Period 1: Insulin Aspart (Fiasp®) administered SC Period 2: LY900014 administered subcutaneously (SC) Period 3: Insulin Aspart (NovoRapid®) administered SC Period 4:Insulin Lispro (Humalog®) administered SC with 21 hours between doses	Period 1: Insulin Aspart (NovoRapid®) administered SC Period 2:Insulin Lispro (Humalog®) administered SC Period 3: insulin Aspart (Fiasp®) administered SC Period 4: LY900014 administered subcutaneously (SC) with 21 hours between doses	Period 1:Insulin Lispro (Humalog®) administered SC Period 2: Insulin Aspart (NovoRapid®) administered SC Period 3: LY900014 administered SC Period 4: insulin Aspart (Fiasp®) administered SC with 21 hours between doses	Healthy participant cohort did not receive any dose of study drug.
Period Title: Period 1
STARTED	17	16	18	17	12
Received at Least 1 Dose of Study Drug	17	16	18	17	0
COMPLETED	17	16	18	17	12
NOT COMPLETED	0	0	0	0	0
Period Title: Period 1
STARTED	17	16	18	17	12
Received at Least 1 Dose of Study Drug	17	16	18	17	0
COMPLETED	17	16	18	17	12
NOT COMPLETED	0	0	0	0	0
Period Title: Period 1
STARTED	17	16	18	17	12
Received at Least 1 Dose of Study Drug	17	15	18	17	0
COMPLETED	17	15	18	17	12
NOT COMPLETED	0	1	0	0	0
Period Title: Period 1
STARTED	17	15	18	17	12
Received at Least 1 Dose of Study Drug	17	15	18	17	0
COMPLETED	17	15	18	17	12
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	T1DM Cohort	Healthy Participants	Total
Arm/Group Description	All randomized participants with T1DM participants who received at least 1 dose of study drug.	All healthy participants.	Total of all reporting groups
Overall Participants	68	12	80
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	61 89.7%	12 100%	73 91.3%
>=65 years	7 10.3%	0 0%	7 8.8%
Sex: Female, Male (Count of Participants)
Female	17 25%	0 0%	17 21.3%
Male	51 75%	12 100%	63 78.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.5%	0 0%	1 1.3%
Not Hispanic or Latino	67 98.5%	12 100%	79 98.8%
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	68 100%	12 100%	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 (participants) [Number]
Germany	68 100%	12 100%	0 0%
Body Mass Index (BMI) (kilograms per meter squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter squared]	25.82 (2.36)	25.38 (1.80)	25.38 (1.80)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro or Insulin Aspart Area Under the Concentration Curve From Zero to Seven Hours (AUC 0-7h) Following Administration of Each Study Arm
Description	PK: Insulin Lispro or Insulin Aspart AUC(0-7h)
Time Frame	0 (predose), 1, 2, 3,5,10, 15, 20, 25, 30,35, 40, 45, 50, 55,60, 70, 90, 120, 150,180, 240, 300, 360 and 420 minutes postdose

Outcome Measure Data

Analysis Population Description

All randomized, T1DM participants who received at least 1 dose of study drug.

Arm/Group Title	LY900014	Insulin Lispro (Humalog®)	Insulin Aspart (NovoRapid®)	Insulin Aspart (Fiasp®)
Arm/Group Description	T1DM participants received a single, individualized, subcutaneous (SC) dose of LY900014	T1DM participants received a single,individualized, SC dose of insulin lispro (Humalog)	T1DM participants received a single,individualized, SC dose of insulin	T1DM participants received a single,individualized, SC dose of insulin aspart
Measure Participants	62	62	62	62
Geometric Mean (Geometric Coefficient of Variation) [picomols times hour per Liter]	786 (36)	756 (37)	938 (41)	928 (36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY900014, Insulin Lispro (Humalog®)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of LS Means
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.985 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT)
Description	PD: AUC(0-5h) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT)
Time Frame	Time Frame:-30, -15, 0 (predose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, and 300 minutes postdose

Outcome Measure Data

Analysis Population Description

All randomized participants who evaluable PD parameters.

Arm/Group Title	LY900014	Insulin Lispro (Humalog®)	Insulin Aspart (NovoRapid®)	Insulin Aspart (Fiasp®)	Healthy Participants
Arm/Group Description	T1DM participants received a single, individualized, subcutaneous (SC) dose of LY900014	T1DM participants received a single,individualized, SC dose of insulin lispro (Humalog®) T1DM participants	T1DM participants received a single,individualized, SC dose of insulin aspart	T1DM participants received a single,individualized, SC dose of insulin aspart	Healthy participants, cohort did not receive study drug.
Measure Participants	67	67	67	67	12
Mean (Standard Deviation) [milligrams times hour per deciliter]	81.5 (212)	141 (224)	157 (243)	101 (226)	44.1 (32.5)

Adverse Events

Time Frame	up to 6 weeks
Arm/Group Title	LY900014		Insulin Lispro (Humalog®)		Insulin Aspart (Fiasp®)		Insulin Aspart (NovoRapid®)		Healthy Participants
Arm/Group Description	T1DM participants received a single, subcutaneous (SC) dose of LY900014.		T1DM participants received a single, SC dose of insulin lispro (Humalog®).		T1DM participants received a single, SC dose of insulin aspart (Fiasp®).		T1DM participants received a single, SC dose of insulin aspart (NovoRapid®).		Healthy subject cohort, cohort did not receive any dose of study drug.
All Cause Mortality
	LY900014		Insulin Lispro (Humalog®)		Insulin Aspart (Fiasp®)		Insulin Aspart (NovoRapid®)		Healthy Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/67 (0%)		0/68 (0%)		0/67 (0%)		0/12 (0%)
Serious Adverse Events
	LY900014		Insulin Lispro (Humalog®)		Insulin Aspart (Fiasp®)		Insulin Aspart (NovoRapid®)		Healthy Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/67 (0%)		0/68 (0%)		0/67 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	LY900014		Insulin Lispro (Humalog®)		Insulin Aspart (Fiasp®)		Insulin Aspart (NovoRapid®)		Healthy Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/67 (0%)		0/68 (0%)		0/67 (0%)		0/12 (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.