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

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
LY2963016
Lantus®
Insulin Lispro
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Insulin Glargine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Peking University Peoples Hospital
  • Shantou University Medical College No.2 Affiliated Hospital
  • Guangdong Province People's Hospital
  • The First Affiliated Hospital, Sun-Yat Sen University
  • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • The 1st Affiliated Hospital of Henan Science and technology
  • Wu Han Tongji Hospital
  • The Second Xiangya Hospital of Central South University
  • Changzhou No.2 People's Hospital
  • The Second Affiliated Hospital of Nanjing Medical University
  • Nanjing First Hospital
  • Affiliated Hospital of Jiangsu University
  • No.2 Hospital Affiliated to Jilin University
  • Dalian Med. Univ. No 2 Affiliate Hospital
  • The First Affiliated Hospital with Nanjing Medical Universit
  • Shanghai Tenth People's Hospital
  • West China Hospital of Sichuan University
  • First People's Hospital of Yunnan Province
  • Peking Union Medical College Hospital
  • Shanghai Putuo District Center Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

LY2963016 + Insulin Lispro

Lantus® + Insulin Lispro

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).
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).
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.
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.
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).
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).
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.
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.
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.
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).
Number of Participants With Detectable Anti-Glargine Antibodies
Number of participants with detectable anti-glargine antibodies
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.

Full Information

First Posted
November 7, 2017
Last Updated
March 3, 2021
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT03338023
Brief Title
A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 1 Diabetes Mellitus
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 15, 2020
Overall Recruitment Status
Completed
Study Start Date
March 23, 2018 (Actual)
Primary Completion Date
March 5, 2020 (Actual)
Study Completion Date
March 5, 2020 (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 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Insulin Glargine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
272 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LY2963016 + Insulin Lispro
Arm Type
Experimental
Arm Description
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.
Arm Title
Lantus® + Insulin Lispro
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
LY2963016
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Lantus®
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Insulin Lispro
Intervention Description
Administered SC
Primary Outcome Measure Information:
Title
Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®)
Description
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).
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016)
Description
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).
Time Frame
Baseline, Week 24
Title
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values
Description
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).
Time Frame
Baseline, Week 24
Title
Percentage of Participants With HbA1c <7%
Description
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time Frame
Week 24
Title
Percentage of Participants With HbA1c ≤6.5%
Description
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time Frame
Week 24
Title
Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG
Description
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).
Time Frame
Baseline, Week 24
Title
Change From Baseline in Glycemic Variability of Fasting Blood Glucose
Description
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).
Time Frame
Baseline, Week 24
Title
Change From Baseline in Basal Insulin Dose
Description
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.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Prandial Insulin Dose
Description
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.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Body Weight
Description
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.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ)
Description
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).
Time Frame
Baseline, Week 24
Title
Number of Participants With Detectable Anti-Glargine Antibodies
Description
Number of participants with detectable anti-glargine antibodies
Time Frame
Baseline through Week 24
Title
Rate of Documented Symptomatic Hypoglycemia
Description
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.
Time Frame
Baseline through Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
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
Peking University Peoples Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Facility Name
Shantou University Medical College No.2 Affiliated Hospital
City
Shantou
State/Province
Guang Dong Province
ZIP/Postal Code
515041
Country
China
Facility Name
Guangdong Province People's Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
The First Affiliated Hospital, Sun-Yat Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510120
Country
China
Facility Name
The 1st Affiliated Hospital of Henan Science and technology
City
Luoyang
State/Province
Henan
ZIP/Postal Code
471003
Country
China
Facility Name
Wu Han Tongji Hospital
City
Wu Han
State/Province
Hu Bei
ZIP/Postal Code
430030
Country
China
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410011
Country
China
Facility Name
Changzhou No.2 People's Hospital
City
Changzhou
State/Province
Jiangsu
ZIP/Postal Code
213003
Country
China
Facility Name
The Second Affiliated Hospital of Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210011
Country
China
Facility Name
Nanjing First Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210012
Country
China
Facility Name
Affiliated Hospital of Jiangsu University
City
Zhenjiang
State/Province
Jiangsu
ZIP/Postal Code
212001
Country
China
Facility Name
No.2 Hospital Affiliated to Jilin University
City
Changchun City
State/Province
Jilin
ZIP/Postal Code
130041
Country
China
Facility Name
Dalian Med. Univ. No 2 Affiliate Hospital
City
Dalian
State/Province
Liao Ning
ZIP/Postal Code
116023
Country
China
Facility Name
The First Affiliated Hospital with Nanjing Medical Universit
City
Nanjing
State/Province
Nanjing
ZIP/Postal Code
210029
Country
China
Facility Name
Shanghai Tenth People's Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200072
Country
China
Facility Name
West China Hospital of Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
First People's Hospital of Yunnan Province
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650034
Country
China
Facility Name
Peking Union Medical College Hospital
City
Beijing
ZIP/Postal Code
88798
Country
China
Facility Name
Shanghai Putuo District Center Hospital
City
Shanghai
ZIP/Postal Code
200062
Country
China

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 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 URL
https://vivli.org/
Citations:
PubMed Identifier
35471721
Citation
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.
Results Reference
derived

Learn more about this trial

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

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