A Study of LY900014 Compared to Insulin Lispro (Humalog) in Adults With Type 1 Diabetes

A Prospective, Randomized, Double-Blind Comparison of LY900014 to Insulin Lispro in Combination With Insulin Glargine or Insulin Degludec in Adults With Type 1 Diabetes

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 1 diabetes (T1D).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: LY900014; Drug: Insulin Glargine; Drug: Insulin Degludec; Drug: Insulin Lispro

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, X5008HHW
    • Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1120AAC
      • Centro Médico Viamonte
    • Caba, Buenos Aires, Argentina, C1056ABJ
      • Centro de Investigaciones Metabólicas (CINME)
• China
  • Beijing, China, 100730
    • Beijing Peking Union Medical College Hospital
  • Shanghai, China, 200062
    • Shanghai Putuo District Center Hospital
  • Shanghai, China, 200092
    • Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
  • Anhui
    • Hefei, Anhui, China, 230011
      • The Second People's Hospital of Hefei
  • Guang Dong Province
    • Shantou, Guang Dong Province, China, 515041
      • Shantou University Medical College No.2 Affiliated Hospital
  • Guangdong
    • Dongguan, Guangdong, China, 523059
      • Dongguan People's Hospital
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Shenzhen, Guangdong, China, 518039
      • Shenzhen Second People's Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Luoyang, Henan, China, 471003
      • The First Affiliated Hospital of Henan University of Science &Technology
  • Hunan
    • Changde, Hunan, China, 415003
      • The First People's Hospital of Changde City
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Changzhou No.2 People's Hospital
    • Nanjing, Jiangsu, China, 210000
      • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
    • Nanjing, Jiangsu, China, 210006
      • The First Hospital of Nanjing
    • Nanjing, Jiangsu, China, 211166
      • Sir Run Run Hospital of Nanjing Medical University
    • Suzhou, Jiangsu, China, 215004
      • The Second Affiliated Hospital of Soochow University
    • Zhenjiang, Jiangsu, China, 212000
      • Affiliated Hospital of Jiangsu University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
    • Changchun City, Jilin, China, 130041
      • No.2 Hospital Affiliated to Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Nanjing
    • Nanjing, Nanjing, China, 210029
      • Jiangsu Province Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200072
      • Shanghai Tenth People's Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital Sichuan University
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44150
      • Unidad de Investigaci�n Cl�nica Cardiometabolica de Occidente
    • Guadalajara, Jalisco, Mexico, 44650
      • Unidad de patologia Clinica
  • N.l.
    • Monterrey, N.l., Mexico, 64460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must have T1D for at least 1 year prior to screening and continuously using insulin for at least 1 year.
• Participants must have HbA1c of ≥7.0 and ≤10.0%.
• Participants must have been treated for at least 90 days prior to screening with either multiple daily injection(s) (MDI) or premixed analog/human insulin regimens at least twice daily.
• Participants must have body mass index (BMI) of ≤35.0 kilograms per square meter (kg/m2).

Exclusion Criteria:

• Participants must not have used other anti-hyperglycemic medications or therapies (inhaled, oral or injectable) except for metformin within 90-days prior to screening.
• Participants must not have had more than 1 severe hypoglycemic episode within 6 months prior to screening.
• Participants must not have had more than 1 hospitalization related to hyperglycemia or diabetic ketoacidosis within 6 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LY900014; 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.	Drug: LY900014; Administered SC; Other Names: Ultra-Rapid Lispro; Drug: Insulin Glargine; Administered SC; Drug: Insulin Degludec; Administered SC
ACTIVE_COMPARATOR: Insulin Lispro (Humalog); Participants received 100 U/mL insulin lispro SC 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily.	Drug: Insulin Glargine; Administered SC; Drug: Insulin Degludec; Administered SC; Drug: Insulin Lispro; Administered SC; Other Names: Humalog; LY275585

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of hemoglobin A. It 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) as variables.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. LS mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares) as variables.	Week 26
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. LS mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares) as variables.	Week 26
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 days.	Baseline through Week 26
Rate of Documented Symptomatic Post Meal Hypoglycemia	Documented symptomatic post meal 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 post meal hypoglycemia per year during a defined period is calculated by the total number of documented symptomatic post meal hypoglycemia events within the period divided by the cumulative days on treatment from all participants within that treatment group *365.25.	Baseline through Week 26
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. It accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. LS mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 26
Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values	SMBG 10-point profiles were measured at morning (premeal-fasting, 1-hour post meal, 2-hour post meal), midday (premeal, 1-hour post meal, 2-hour post meal), evening (premeal, 1-hour post meal, 2-hour post meal) and bedtime. LS Mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 26
Change From Baseline in Daily Insulin Dose	LS mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 26
Percentage of Participants With HbA1c <7% and ≤6.5%	HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 26

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY900014 Compared to Insulin Lispro (Humalog) in Adults With Type 1 Diabetes

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 29, 2019
• Primary Completion (ACTUAL): January 10, 2022
• Study Completion (ACTUAL): January 10, 2022

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (ACTUAL): May 16, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro
• Other Study ID Numbers: 16829; I8B-FH-ITSD (OTHER: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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