Back to resultsA Study of LY900014 Compared to Insulin Lispro (Humalog) in Adults With Type 2 Diabetes
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LY900014
Insulin Lispro
Insulin Glargine
Insulin Degludec
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Participants must have T2D based on the disease diagnostic criteria World Health Organization (WHO) classification.
- Participants must have been treated for at least 90 days prior to screening with either basal insulin + at least 1 prandial injection of bolus insulin or premixed analog/human insulin regimens at least twice daily.
- Participants must be treated no more than 3 oral anti-hyperglycemic medications (OAMs).
- Participants must have a HbA1c ≥7.0% and ≤11.0%.
- Participants must have body mass index (BMI) of ≤35.0 kilograms per meter squared (kg/m2).
Exclusion Criteria:
- Participants must not have been diagnosed, at any time, with type 1 diabetes (T1D) or latent autoimmune diabetes in adults.
- Participants must not have had any episode of severe hypoglycemia within the 6 months prior to screening.
- Participants must not have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening.
- Participants must not have used thiazolidinediones, glucagon-like peptide 1 (GLP-1) receptor agonist, or pramlintide within 90 days prior to screening.
Sites / Locations
- Centro Médico Viamonte
- Centro de Investigaciones Metabólicas (CINME)
- Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
- Beijing Pinggu District Hospital
- Tianjin Medical University General Hospital
- Cangzhou People's Hospital
- The First Hospital of Qinhuangdao
- Inner Mongolia People's Hospital
- Dalian Municipal Central Hospital Affiliated of Dalian Medical University
- Shengjing Hospital of China Medical University
- Shanghai Putuo District Center Hospital
- Shanghai 6th people's hospital
- The Affiliated Jiangyin Hospital of Southeast University Medical College
- Zhongda Hospital Southeast University
- Nanjing Medical University - Nanjing Jiangning Hospital
- Affiliated Hospital of Jiangsu University
- The Third Hospital of Nanchang
- The Central Hospital of Wuhan
- The First People's Hospital of Yueyang
- Chongqing General Hospital
- Fujian Medical University Union Hospital
- Xingtai People's Hospital
- The Fourth Affiliated Hospital of Harbin Medical University
- The First Hospital of Qiqihar
- The First Affiliated Hospital of Henan University of Science &Technology
- Wuhan Pu'ai Hospital
- Yichang Central People's Hospital
- Chenzhou NO.1 People's Hospital
- Changzhou No.2 People's Hospital
- The First Hospital of Nanjing
- China-Japan Union Hospital, CJUH.
- Siping Central People's Hospital
- Qinghai University Affiliated Hospital
- Jinan Central Hospital
- The First Affiliated Hospital of Xi'an Medical University
- Beijing Peking Union Medical College Hospital
- Pingxiang People's Hospital
- Unidad de patologia Clinica
- Centro de Inv. Medica de Occidente, SC
- Unidad Médica para la Salud Integral
- Hospital Universitario Dr. Jose Eleuterio Gonzalez
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
LY900014
Insulin Lispro
Arm Description
Participants received 100 units per milliliter (U/mL) LY900014 subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily.
Participants received 100 U/mL insulin lispro (Humalog) given SC 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily.
Outcomes
Primary Outcome Measures
Change From Baseline in Hemoglobin A1c (HbA1c)
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Pooled Country + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares).
Secondary Outcome Measures
1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT)
A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 1-hour timepoint after the start of meal minus fasting serum glucose. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares).
2-hour PPG Excursion During MMTT
A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 2-hour timepoint after the start of meal minus fasting serum glucose. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares).
Rate of Severe Hypoglycemia
Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within that treatment group *36525.
Rate of Documented Symptomatic Postmeal Hypoglycemia
Documented symptomatic postmeal hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of ≤70 mg/dL [3.9 millimole per liter (mmol/L)]. The rate of documented symptomatic postmeal hypoglycemia was estimated by negative binomial model: number of episodes = treatment with log (treatment exposure in days/365.25) as an offset variable
Change From Baseline in 1,5-Anhydroglucitol (1,5-AG)
1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. 1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. LS Mean was calculated using mixed model repeated measures (MMRM) with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares)
Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values
SMBG 10-point profiles were measured at fasting, 1-hour post morning meal, 2-hours post morning meal, pre midday meal, 1-hour post midday meal, 2-hours post midday meal, pre evening meal, 1-hour post evening meal, 2-hours post evening meal, and bedtime. LS Mean was analyzed using mixed model repeated measures (MMRM) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares).
Change From Baseline in Insulin Dose
LS mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares)
Percentage of Participants With HbA1c <7% and ≤6.5%
Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Only subjects with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03952143
Brief Title
A Study of LY900014 Compared to Insulin Lispro (Humalog) in Adults With Type 2 Diabetes
Official Title
A Prospective, Randomized, Double-Blind Comparison of LY900014 to Insulin Lispro, Both in Combination With Insulin Glargine or Insulin Degludec in Adults With Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
May 27, 2019 (Actual)
Primary Completion Date
January 20, 2021 (Actual)
Study Completion Date
January 20, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to see if LY900014 compared to insulin lispro (Humalog), both in combination with insulin glargine or insulin degludec, is safe and effective in participants with type 2 diabetes (T2D).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
628 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LY900014
Arm Type
Experimental
Arm Description
Participants received 100 units per milliliter (U/mL) LY900014 subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily.
Arm Title
Insulin Lispro
Arm Type
Active Comparator
Arm Description
Participants received 100 U/mL insulin lispro (Humalog) given SC 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily.
Intervention Type
Drug
Intervention Name(s)
LY900014
Other Intervention Name(s)
Ultra-Rapid Lispro
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Insulin Lispro
Other Intervention Name(s)
LY275585, Humalog
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Insulin Glargine
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Insulin Degludec
Intervention Description
Administered SC
Primary Outcome Measure Information:
Title
Change From Baseline in Hemoglobin A1c (HbA1c)
Description
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Pooled Country + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares).
Time Frame
Baseline, Week 26
Secondary Outcome Measure Information:
Title
1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT)
Description
A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 1-hour timepoint after the start of meal minus fasting serum glucose. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares).
Time Frame
Week 26
Title
2-hour PPG Excursion During MMTT
Description
A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 2-hour timepoint after the start of meal minus fasting serum glucose. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares).
Time Frame
Week 26
Title
Rate of Severe Hypoglycemia
Description
Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within that treatment group *36525.
Time Frame
Baseline through Week 26
Title
Rate of Documented Symptomatic Postmeal Hypoglycemia
Description
Documented symptomatic postmeal hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of ≤70 mg/dL [3.9 millimole per liter (mmol/L)]. The rate of documented symptomatic postmeal hypoglycemia was estimated by negative binomial model: number of episodes = treatment with log (treatment exposure in days/365.25) as an offset variable
Time Frame
Baseline through Week 26
Title
Change From Baseline in 1,5-Anhydroglucitol (1,5-AG)
Description
1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. 1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. LS Mean was calculated using mixed model repeated measures (MMRM) with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares)
Time Frame
Baseline, Week 26
Title
Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values
Description
SMBG 10-point profiles were measured at fasting, 1-hour post morning meal, 2-hours post morning meal, pre midday meal, 1-hour post midday meal, 2-hours post midday meal, pre evening meal, 1-hour post evening meal, 2-hours post evening meal, and bedtime. LS Mean was analyzed using mixed model repeated measures (MMRM) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares).
Time Frame
Baseline, Week 26
Title
Change From Baseline in Insulin Dose
Description
LS mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares)
Time Frame
Baseline, Week 26
Title
Percentage of Participants With HbA1c <7% and ≤6.5%
Description
Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Only subjects with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.
Time Frame
Week 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants must have T2D based on the disease diagnostic criteria World Health Organization (WHO) classification.
Participants must have been treated for at least 90 days prior to screening with either basal insulin + at least 1 prandial injection of bolus insulin or premixed analog/human insulin regimens at least twice daily.
Participants must be treated no more than 3 oral anti-hyperglycemic medications (OAMs).
Participants must have a HbA1c ≥7.0% and ≤11.0%.
Participants must have body mass index (BMI) of ≤35.0 kilograms per meter squared (kg/m2).
Exclusion Criteria:
Participants must not have been diagnosed, at any time, with type 1 diabetes (T1D) or latent autoimmune diabetes in adults.
Participants must not have had any episode of severe hypoglycemia within the 6 months prior to screening.
Participants must not have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening.
Participants must not have used thiazolidinediones, glucagon-like peptide 1 (GLP-1) receptor agonist, or pramlintide within 90 days prior to screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Centro Médico Viamonte
City
Buenos Aires
State/Province
Ar-c
ZIP/Postal Code
C1120AAC
Country
Argentina
Facility Name
Centro de Investigaciones Metabólicas (CINME)
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1056ABJ
Country
Argentina
Facility Name
Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
City
Cordoba
ZIP/Postal Code
X5008HHW
Country
Argentina
Facility Name
Beijing Pinggu District Hospital
City
Beijing
State/Province
Cn-11
ZIP/Postal Code
101200
Country
China
Facility Name
Tianjin Medical University General Hospital
City
Tianjin
State/Province
Cn-12
ZIP/Postal Code
300052
Country
China
Facility Name
Cangzhou People's Hospital
City
Cangzhou
State/Province
Cn-13
ZIP/Postal Code
061000
Country
China
Facility Name
The First Hospital of Qinhuangdao
City
Qinhuangdao Shi
State/Province
Cn-13
ZIP/Postal Code
066000
Country
China
Facility Name
Inner Mongolia People's Hospital
City
Hohhot
State/Province
Cn-15
ZIP/Postal Code
010017
Country
China
Facility Name
Dalian Municipal Central Hospital Affiliated of Dalian Medical University
City
Dalian
State/Province
Cn-21
ZIP/Postal Code
116033
Country
China
Facility Name
Shengjing Hospital of China Medical University
City
Shenyang
State/Province
Cn-21
ZIP/Postal Code
110004
Country
China
Facility Name
Shanghai Putuo District Center Hospital
City
Shanghai
State/Province
Cn-31
ZIP/Postal Code
200062
Country
China
Facility Name
Shanghai 6th people's hospital
City
Shanghai
State/Province
Cn-31
Country
China
Facility Name
The Affiliated Jiangyin Hospital of Southeast University Medical College
City
Jiangyin
State/Province
Cn-32
ZIP/Postal Code
214400
Country
China
Facility Name
Zhongda Hospital Southeast University
City
Nanjing
State/Province
Cn-32
ZIP/Postal Code
210009
Country
China
Facility Name
Nanjing Medical University - Nanjing Jiangning Hospital
City
Nanjing
State/Province
Cn-32
ZIP/Postal Code
211100
Country
China
Facility Name
Affiliated Hospital of Jiangsu University
City
Zhenjiang
State/Province
Cn-32
ZIP/Postal Code
212000
Country
China
Facility Name
The Third Hospital of Nanchang
City
Nanchang
State/Province
Cn-36
ZIP/Postal Code
330009
Country
China
Facility Name
The Central Hospital of Wuhan
City
Wuhan
State/Province
Cn-42
Country
China
Facility Name
The First People's Hospital of Yueyang
City
Yueyang
State/Province
Cn-43
ZIP/Postal Code
414000
Country
China
Facility Name
Chongqing General Hospital
City
Chongqing
State/Province
Cn-50
ZIP/Postal Code
400014
Country
China
Facility Name
Fujian Medical University Union Hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350001
Country
China
Facility Name
Xingtai People's Hospital
City
Xingtai
State/Province
Hebei
ZIP/Postal Code
054031
Country
China
Facility Name
The Fourth Affiliated Hospital of Harbin Medical University
City
Harbin
State/Province
Heilongjiang
ZIP/Postal Code
150001
Country
China
Facility Name
The First Hospital of Qiqihar
City
Qiqihar
State/Province
Heilongjiang
ZIP/Postal Code
161006
Country
China
Facility Name
The First Affiliated Hospital of Henan University of Science &Technology
City
Luoyang
State/Province
Henan
ZIP/Postal Code
471003
Country
China
Facility Name
Wuhan Pu'ai Hospital
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Facility Name
Yichang Central People's Hospital
City
Yichang
State/Province
Hubei
ZIP/Postal Code
443003
Country
China
Facility Name
Chenzhou NO.1 People's Hospital
City
Chenzhou
State/Province
Hunan
ZIP/Postal Code
424300
Country
China
Facility Name
Changzhou No.2 People's Hospital
City
Changzhou
State/Province
Jiangsu
ZIP/Postal Code
213003
Country
China
Facility Name
The First Hospital of Nanjing
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210012
Country
China
Facility Name
China-Japan Union Hospital, CJUH.
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130033
Country
China
Facility Name
Siping Central People's Hospital
City
Siping
State/Province
Jilin
ZIP/Postal Code
136000
Country
China
Facility Name
Qinghai University Affiliated Hospital
City
Xining
State/Province
Qinghai
ZIP/Postal Code
810001
Country
China
Facility Name
Jinan Central Hospital
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250013
Country
China
Facility Name
The First Affiliated Hospital of Xi'an Medical University
City
XI 'an
State/Province
Shanxi
Country
China
Facility Name
Beijing Peking Union Medical College Hospital
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Pingxiang People's Hospital
City
Pingxiang
ZIP/Postal Code
337000
Country
China
Facility Name
Unidad de patologia Clinica
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44650
Country
Mexico
Facility Name
Centro de Inv. Medica de Occidente, SC
City
Zapopan
State/Province
Jalisco
ZIP/Postal Code
45116
Country
Mexico
Facility Name
Unidad Médica para la Salud Integral
City
San Nicolás de los Garza
State/Province
Mx-nle
ZIP/Postal Code
66465
Country
Mexico
Facility Name
Hospital Universitario Dr. Jose Eleuterio Gonzalez
City
Monterrey
State/Province
N.l.
ZIP/Postal Code
64460
Country
Mexico
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
https://vivli.org/
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/6hfa0kzMFqmoyoC8Nn6bXD
Description
A Study of Compared to Insulin Lispro (Humalog) in Adults With Type 2 Diabetes
Learn more about this trial
A Study of LY900014 Compared to Insulin Lispro (Humalog) in Adults With Type 2 Diabetes
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