A Study of LY900014 Compared to Insulin Lispro (Humalog) in Adults With Type 2 Diabetes

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

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: LY900014; Drug: Insulin Glargine; Drug: Insulin Degludec; Drug: Insulin Lispro

• Study Type: Interventional
• Enrollment (Actual): 628
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, X5008HHW
    • Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
  • Ar-c
    • Buenos Aires, Ar-c, Argentina, C1120AAC
      • Centro Médico Viamonte
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1056ABJ
      • Centro de Investigaciones Metabólicas (CINME)
• China
  • Beijing, China, 100730
    • Beijing Peking Union Medical College Hospital
  • Pingxiang, China, 337000
    • Pingxiang People's Hospital
  • Cn-11
    • Beijing, Cn-11, China, 101200
      • Beijing Pinggu District Hospital
  • Cn-12
    • Tianjin, Cn-12, China, 300052
      • Tianjin Medical University General Hospital
  • Cn-13
    • Cangzhou, Cn-13, China, 061000
      • Cangzhou People's Hospital
    • Qinhuangdao Shi, Cn-13, China, 066000
      • The First Hospital of Qinhuangdao
  • Cn-15
    • Hohhot, Cn-15, China, 010017
      • Inner Mongolia People's Hospital
  • Cn-21
    • Dalian, Cn-21, China, 116033
      • Dalian Municipal Central Hospital Affiliated of Dalian Medical University
    • Shenyang, Cn-21, China, 110004
      • Shengjing Hospital of China Medical University
  • Cn-31
    • Shanghai, Cn-31, China, 200062
      • Shanghai Putuo District Center Hospital
    • Shanghai, Cn-31, China
      • Shanghai 6th People's Hospital
  • Cn-32
    • Jiangyin, Cn-32, China, 214400
      • The Affiliated Jiangyin Hospital of Southeast University Medical College
    • Nanjing, Cn-32, China, 210009
      • Zhongda Hospital Southeast University
    • Nanjing, Cn-32, China, 211100
      • Nanjing Medical University - Nanjing Jiangning Hospital
    • Zhenjiang, Cn-32, China, 212000
      • Affiliated Hospital of Jiangsu University
  • Cn-36
    • Nanchang, Cn-36, China, 330009
      • The Third Hospital of Nanchang
  • Cn-42
    • Wuhan, Cn-42, China
      • The Central Hospital of Wuhan
  • Cn-43
    • Yueyang, Cn-43, China, 414000
      • The First People's Hospital of Yueyang
  • Cn-50
    • Chongqing, Cn-50, China, 400014
      • Chongqing General Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Hebei
    • Xingtai, Hebei, China, 054031
      • Xingtai People's Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Affiliated Hospital of Harbin Medical University
    • Qiqihar, Heilongjiang, China, 161006
      • The First Hospital of Qiqihar
  • Henan
    • Luoyang, Henan, China, 471003
      • The First Affiliated Hospital of Henan University of Science &Technology
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Wuhan Pu'ai Hospital
    • Yichang, Hubei, China, 443003
      • Yichang Central People's Hospital
  • Hunan
    • Chenzhou, Hunan, China, 424300
      • Chenzhou No.1 People's Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Changzhou No.2 People's Hospital
    • Nanjing, Jiangsu, China, 210012
      • The First Hospital of Nanjing
  • Jilin
    • Changchun, Jilin, China, 130033
      • China-Japan Union Hospital, CJUH.
    • Siping, Jilin, China, 136000
      • Siping Central People's Hospital
  • Qinghai
    • Xining, Qinghai, China, 810001
      • Qinghai University Affiliated Hospital
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • Shanxi
    • XI 'an, Shanxi, China
      • The First Affiliated Hospital of Xi'an Medical University
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Unidad de patologia Clinica
    • Zapopan, Jalisco, Mexico, 45116
      • Centro de Inv. Medica de Occidente, SC
  • Mx-nle
    • San Nicolás de los Garza, Mx-nle, Mexico, 66465
      • Unidad Médica para la Salud Integral
  • N.l.
    • Monterrey, N.l., Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• 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; 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.	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. 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).	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. 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).	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. 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).	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.	Baseline through Week 26
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	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. 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)	Baseline, Week 26
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).	Baseline, Week 26
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)	Baseline, Week 26
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.	Week 26

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of Compared to Insulin Lispro (Humalog) in Adults With Type 2 Diabetes

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2019
• Primary Completion (Actual): January 20, 2021
• Study Completion (Actual): January 20, 2021

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, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro
• Other Study ID Numbers: 16830; I8B-FH-ITSE (Other Identifier: 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; Statistical Analysis Plan (SAP); Clinical Study Report (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