A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 2 Diabetes Mellitus

A Prospective, Randomized, Open-Label Comparison of a Long-Acting Basal Insulin Analog LY2963016 to Lantus® in Adult Chinese Patients With Type 2 Diabetes Mellitus

The purpose of this study is to compare long-acting basal insulin analog LY2963016 to Lantus® in insulin naïve adult Chinese participants with Type 2 Diabetes Mellitus (T2DM) on 2 or more oral antihyperglycemic medications (OAMs). Participants will continue their OAMs throughout the study.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: LY2963016; Drug: Lantus®

• Study Type: Interventional
• Enrollment (Actual): 536
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 88798
    • Peking Union Medical College Hospital
  • Chongqing, China, 400013
    • Chongqing General Hospital
  • Shanghai, China, 200062
    • Shanghai Putuo District Center Hospital
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Affiliated Hospital of Lanzhou University
  • Guang Dong Province
    • Shantou, Guang Dong Province, China, 515041
      • Shantou University Medical College No.2 Affiliated Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Province People's Hospital
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun-Yat Sen University
  • Henan
    • Luoyang, Henan, China, 471003
      • The 1st Affiliated Hospital of Henan Science and technology
  • Hubei
    • Wu Han, Hubei, China, 430030
      • Tongji Hosp Tongji Med Col Huazhong Univ of Sci & Tech
    • Wuhan, Hubei, China, 430014
      • Wuhan Central Hospital
  • Hunan
    • Yueyang, Hunan, China, 414000
      • The First People Hospital of Yueyang
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Changzhou No.2 People's Hospital
    • Jiangyin, Jiangsu, China, 214400
      • The Affliated Jiangyin Hospital of Southeast University Medical College
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210012
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hosp Affiliated Hosp of Nanjing Univ Med
    • Nanjing, Jiangsu, China, 211199
      • Nanjing Jiangning Hospital
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
    • Xuzhou, Jiangsu, China, 221009
      • Xuzhou Central Hospital
    • Zhenjiang, Jiangsu, China, 212001
      • Affiliated Hospital of Jiangsu University
  • Jilin
    • Changchun City, Jilin, China, 130041
      • No.2 Hospital Affiliated to Jilin University
    • Siping, Jilin, China, 136000
      • Siping Central People's Hospital
  • Liao Ning
    • Dalian, Liao Ning, China, 116023
      • Dalian Med. Univ. No 2 Affiliate Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110022
      • Shengjing Hospital of China Medical University
  • Nanjing
    • Nanjing, Nanjing, China, 210029
      • The First Affiliated Hospital with Nanjing Medical Universit
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shan XI
    • Tai Yuan, Shan XI, China, 030001
      • 1st Affiliated Hospital of Shanxi Medical University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University

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:

• Have T2DM based on the disease diagnostic criteria World Health Organization (WHO) classification.
• Have been receiving 2 or more OAMs at stable doses for the 12 weeks prior to screening.
• Have a HbA1c ≥7.0% and ≤11.0%.
• Body mass index (BMI) ≤35 kilograms per meter squared.

Exclusion Criteria:

• Have used insulin therapy (outside of pregnancy) anytime in the past 1 year, except for short-term treatment of acute conditions, and up to a maximum of 4 continuous weeks.
• Have used any glucagon like peptide (GLP-1) receptor agonists within the previous 90 days.
• Are currently taking traditional medicine (herbal medicine or patent medicine) with known/specified content of anti-hyperglycemic effects within 3 months before screening.
• Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
• Have had ≥2 emergency room visits or hospitalizations due to poor glucose control.
• Have known hypersensitivity or allergy to Lantus® or its excipients.
• Are receiving chronic systemic glucocorticoid therapy at pharmacological doses or have received such therapy within 4 weeks immediately preceding screening.
• Have obvious signs or symptoms, or laboratory evidence, of liver disease.
• Have one of the following concomitant diseases: significant cardiac or gastrointestinal disease.
• Have a history of renal transplantation, are currently receiving renal dialysis or have a serum creatinine greater than 2.0 milligrams per deciliter.
• Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia.
• Participants with active cancer or personal history of cancer within the previous 5 years.
• Are pregnant or intend to become pregnant during the course of the study.
• Are women who are breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2963016; Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the fasting blood glucose (FBG) ≤100 milligram per deciliter (mg/dL) (5.6 millimoles per litre [mmol/L]) while avoiding hypoglycemia. Participants were allowed to continue oral antihyperglycemic medication (OAM).	Drug: LY2963016; Administered SC
Active Comparator: Lantus®; Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM.	Drug: Lantus®; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 to Lantus®)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated by mixed-effects model for repeated measures (MMRM) with baseline, insulin secretagogues at study entry, treatment, visit and treatment*visit in the model.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c (Lantus® to LY2963016)	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, treatment, visit and treatment*visit in the model.	Baseline, Week 24
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values	Seven-point SMBG are completed at the following timepoints: Before Morning Meal, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, 2 Hours After Evening Meal and Bed Time. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.	Baseline, Week 24
Percentage of Participants With HbA1c <7% at Week 24	The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.	Week 24
Percentage of Participants With HbA1c ≤6.5% at Week 24	The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.	Week 24
Change From Baseline in Glycemic Variability of Fasting Blood Glucose	Glycemic variability is measured by the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning and daily pre-meal blood glucose value from the 7-point self-monitoring blood glucose [SMBG] profiles. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.	Baseline, Week 24
Basal Insulin Dose Units Per Day	Units of basal insulin dose taken per day (U/day). LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.	At Week 24
Change From Baseline in Basal Insulin Dose Units Per Day	Units of basal insulin dose taken per day (U/day). LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.	Baseline, Week 24
Change From Baseline in Body Weight	Change from baseline in body weight was evaluated. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.	Baseline, Week 24
Insulin Treatment Satisfaction Questionnaire (ITSQ)	ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. Items divided into 5 domains of satisfaction: Inconvenience of Regimen [(IR) 5 items: domain scores range (DSR) 5-35], Lifestyle Flexibility [(LF) 3 items: DSR 3-21], Glycemic Control [(GC) 3 items: DSR 3-21], Hypoglycemic Control [(HC) 5 items: DSR 5-35], Insulin Delivery Device [(IDD) 6 items: DSR 6-42]. All items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. ITSQ Total Overall Raw Scores range from 22-154. Both raw domain and overall scores are transformed on a scale of 0-100, where transformed score=100*[(7-mean raw score)/6]. Higher scores indicate better treatment satisfaction. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.	At Week 24
Number of Participants With Detectable Anti-Glargine Antibodies	Number of participants with detectable anti-glargine antibodies were reported.	Baseline through 24 weeks
Rate of Total Symptomatic and Nocturnal Hypoglycemia Events (Adjusted by 1 Year)	Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). The overall yearly rates (events/participant/year) of those hypoglycemic events, calculated as, for each participant, the number of episodes times 365.25 and then divided by the participants treatment duration, will be summarized, and analyzed by a negative-binomial regression model with treatment as fixed effects and log of (participant's treatment duration/365.25) as an offset variable. A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking.	Baseline through 24 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Actual): March 18, 2020
• Study Completion (Actual): March 18, 2020

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Insulin glargine
• 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 Glargine
• Other Study ID Numbers: 16037 (Promobilia); I4L-GH-ABET (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 European union (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