A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 1 Diabetes Mellitus

A Prospective, Randomized, Open-Label Comparison of a Long-Acting Basal Insulin Analog, LY2963016, to Lantus® in Combination With Mealtime Insulin Lispro in Adult Chinese Patients With Type 1 Diabetes Mellitus

The purpose of this study is to compare long-acting basal insulin analog LY2963016 to Lantus® in combination with mealtime insulin lispro in adult Chinese participants with Type 1 Diabetes Mellitus (T1DM).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Insulin Lispro; Drug: LY2963016; Drug: Lantus®

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 88798
    • Peking Union Medical College Hospital
  • Shanghai, China, 200062
    • Shanghai Putuo District Center Hospital
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University Peoples Hospital
  • 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
  • Hu Bei
    • Wu Han, Hu Bei, China, 430030
      • Wu Han Tongji Hospital
  • Hunan
    • 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, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210012
      • Nanjing First Hospital
    • Zhenjiang, Jiangsu, China, 212001
      • Affiliated Hospital of Jiangsu University
  • Jilin
    • Changchun City, Jilin, China, 130041
      • No.2 Hospital Affiliated to Jilin University
  • Liao Ning
    • Dalian, Liao Ning, China, 116023
      • Dalian Med. Univ. No 2 Affiliate Hospital
  • Nanjing
    • Nanjing, Nanjing, China, 210029
      • The First Affiliated Hospital with Nanjing Medical Universit
  • Shanghai
    • Shanghai, Shanghai, China, 200072
      • Shanghai Tenth People's Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
  • Yunnan
    • Kunming, Yunnan, China, 650034
      • First People's Hospital of Yunnan Province

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 T1DM based on the disease diagnostic criteria (World Health Organization [WHO] Classification).
• Have duration of T1DM ≥1 year.
• Have HbA1c ≤11 %.
• Have been administered with basal-bolus insulins or pre-mixed insulins for at least 90 days prior to screening.
• Have a body mass index (BMI) ≤35 kilograms per meter squared.

Exclusion Criteria:

• Exposure to an insulin glargine other than Lantus® within previous 30 days.
• Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
• Have had more than one episode of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within 6 months prior to entry into the study.
• Have known hypersensitivity or allergy to any of the study insulins (Lantus® or insulin lispro) or to excipients of the study insulins.
• Are pregnant, intend to become pregnant during the course of the study.
• Women who are breastfeeding.
• Are currently taking traditional medicine (herbal medicine or patent medicine) with known/specified content of anti-hyperglycemic effects within 3 months before screening.
• Have congestive heart failure Class III and IV.
• Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease.
• Have any active cancer.
• Have a history or diagnosis of human immunodeficiency virus (HIV) infection.
• Have presence of clinically significant gastrointestinal disease.
• Have a history of renal transplantation, or are currently receiving renal dialysis.
• Are receiving chronic systemic glucocorticoid therapy at pharmacological doses.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2963016 + Insulin Lispro; Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal.	Drug: Insulin Lispro; Administered SC; Drug: LY2963016; Administered SC
Active Comparator: Lantus® + Insulin Lispro; Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal.	Drug: Insulin Lispro; Administered SC; 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 Noninferior to Lantus®)	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated using mixed-effects model for repeated measures (MMRM) with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time*Treatment (Type III sum of squares).	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c (Lantus® Noninferior 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 using MMRM with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time*Treatment (Type III sum of squares).	Baseline, Week 24
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values	The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Before Morning Meal Glucose, 2 Hours After Morning Meal Glucose, Before Mid-Day Meal Glucose, 2 Hours After Mid-Day Meal Glucose, Before Evening Meal Glucose, Bedtime Glucose and 0300 Am Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 24
Percentage of Participants With HbA1c <7%	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.	Week 24
Percentage of Participants With HbA1c ≤6.5%	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.	Week 24
Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG	Change From Baseline in Intrapatient blood glucose (BG). LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 24
Change From Baseline in Glycemic Variability of Fasting Blood Glucose	Change From Baseline in Glycemic Variability of Fasting Blood Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 24
Change From Baseline in Basal Insulin Dose	Change from baseline in basal insulin dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.	Baseline, Week 24
Change From Baseline in Prandial Insulin Dose	Prandial Insulin Dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.	Baseline, Week 24
Change From Baseline in Body Weight	Change from baseline in body weight. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.	Baseline, Week 24
Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ)	The ITSQ is a validated 22-item questionnaire that was used to assess treatment satisfaction. Items were measured on a 7-point scale, with lower scores reflecting better outcomes. In addition to an overall score, scores were also obtained for 5 domains, including inconvenience of regimen, lifestyle flexibility, glycemic control, hypoglycemic control, and insulin delivery device. Raw domain and overall scores were transformed on a scale from 0 to 100, where a higher score indicated better treatment satisfaction. LS mean was calculated using ANCOVA with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment (Type III sum of squares).	Baseline, Week 24
Number of Participants With Detectable Anti-Glargine Antibodies	Number of participants with detectable anti-glargine antibodies	Baseline through Week 24
Rate of Documented Symptomatic Hypoglycemia	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 (patient's treatment duration/365.25) as an offset variable.	Baseline through Week 24

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Yan X, Feng C, Lou Y, Zhou Z. Efficacy and Safety of LY2963016 Insulin Glargine in Chinese Patients with Type 1 Diabetes Previously Treated with Insulin Glargine (Lantus(R)): a Post Hoc Analysis of a Randomized, Open-Label, Phase 3 Trial. Diabetes Ther. 2022 Jun;13(6):1161-1174. doi: 10.1007/s13300-022-01262-8. Epub 2022 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2018
• Primary Completion (Actual): March 5, 2020
• Study Completion (Actual): March 5, 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): March 29, 2021
• Last Update Submitted That Met QC Criteria: March 3, 2021
• Last Verified: April 15, 2020

More Information

Terms related to this study

• Keywords: Insulin Glargine
• 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 Lispro
• Other Study ID Numbers: 16036; I4L-GH-ABES (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 asigned 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