A Study of Basal Insulin Analog and Insulin Analog Mid Mixture in Chinese Participants With Type 2 Diabetes Mellitus (CLASSIC)

Comparison Between Basal Insulin Analog and Insulin Analog Mid Mixture AS Starter Insulin for Chinese Patients With Type 2 Diabetes Mellitus (CLASSIC Study)

The purpose of this study is to compare the effectiveness of basal insulin analog and insulin analog mid mixture in Chinese participants with type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin Analog Mid Mixture; Drug: Basal Insulin Analog

• Study Type: Interventional
• Enrollment (Actual): 814
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 102206
    • Peking University International Hospital
  • Beijing, China
    • Beijing Hai Dian Hospital
  • Shanghai, China, 200090
    • Shanghai Yangpu District Central Hospital
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University Peoples Hospital
    • Beijing, Beijing, China, 100016
      • Beijing Huaxin Hospital
    • Chaoyang, Beijing, China, 100028
      • China Meitan General Hospital
    • Fangshan, Beijing, China, 102500
      • Beijing Yanhua Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • The 2nd Hospital of Lanzhou University
  • Guangdong
    • Shenzhen, Guangdong, China, 518020
      • Shenzhen City People Hospital
    • Yuexiu, Guangdong, China, 510080
      • The 1st Hospital with Guangdong Pharmaceutical University
  • Henan
    • Luoyang, Henan, China, 471003
      • The 1st Affiliated Hospital of Henan Science and technology
    • Zhengzhou, Henan, China, 450003
      • People's Hospital of Henan Province
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union (Xiehe) Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Changzhou No.2 People's Hospital
    • Nanjing, Jiangsu, China, 210001
      • Nanjing TCM hospital
    • Nanjing, Jiangsu, China, 210024
      • Jiang Su Province Official Hospital
    • Nanjing, Jiangsu, China, 210048
      • Nanjing Jiangbei Hospital
    • Nanjing, Jiangsu, China, 211100
      • Nanjing Jiangning Hospital
    • Taizhou, Jiangsu, China, 225300
      • Taizhou City People Hospital
    • Wuxi, Jiangsu, China, 214000
      • The Second People's Hospital of Wuxi
    • Xuzhou, Jiangsu, China, 221009
      • Xuzhou Central Hospital
  • Shandong
    • Qingdao, Shandong, China, 266071
      • Qingdao Municipal Hospital
    • Taian, Shandong, China, 271000
      • Taian City Central Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200135
      • Shanghai Pudong New Area Gongli Hospital
    • Shanghai, Shanghai, China, 201318
      • Shanghai Pudong New District Zhoupu Hospital
  • Shunqing
    • Nanchong, Shunqing, China, 637000
      • Affiliated Hospital of North Sichuan Medical College
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • The Third Affiliated Hospital of Chengdu University of TCM
    • Luzhou, Sichuan, China, 646000
      • Southwest Medical University Affiliated Hospital
  • Tianjin
    • Nankai, Tianjin, China, 300192
      • Tianjin First Central Hospital
  • Tongzhou
    • Beijing, Tongzhou, China, 101149
      • Beijing Luhe Hospital Capital Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital
    • Ningbo, Zhejiang, China, 315010
      • Ningbo First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• have type 2 diabetes as defined by World Health Organization (WHO) criteria
• are taking oral anti-hyperglycemic medications (OAMs) and are judged as OAM failure by the investigator
• most recent HbA1c value ≥7.5% within 12 weeks of study entry
• in the opinion of the investigator, require to initiate premix analog or basal insulin analog treatment
• willing to start with insulin treatment

Exclusion Criteria:

• have a diagnosis of type 1 diabetes
• have received any type of insulin within 24 months of study entry (except for intermittent use of insulin of less than 1 month each time)
• have serious preexisting medical or other conditions that, in the judgment of the investigator, would preclude participation in this study
• are pregnant or breastfeeding, or intend to become pregnant during the course of the study
• are currently enrolled or have participated, within the last 30 days in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible

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: Insulin Analog Mid Mixture; Insulin analog mid mixture given subcutaneously (SC).	Drug: Insulin Analog Mid Mixture; Administered SC
Experimental: Basal Insulin Analog; Basal insulin analog given SC.	Drug: Basal Insulin Analog; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 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 analysis of covariance (ANCOVA) model with last observation carried forward (LOCF) and with terms for change from baseline in HbA1c as response, treatment as fixed effect and baseline HbA1c as covariate.	Baseline, 24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 48 in 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 ANCOVA model with LOCF and with terms for change from baseline in HbA1c as response, treatment as fixed effect and baseline HbA1c as covariate.	Baseline, 48 Weeks
Percentage of Participants Who Achieve HbA1c <7% at Week 24	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	24 Weeks
Percentage of Participants Who Achieve HbA1c <7% at Week 48	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	48 Weeks
Change From Baseline to Week 24 in Venous Fasting Plasma Glucose	Fasting Plasma glucose (FPG) is a test to determine how much glucose (sugar) is in a plasma sample after an overnight fast. Least Squares (LS) means was determined by ANCOVA model with LOCF and with terms for change from baseline in Venous FPG as response, treatment as fixed effect and baseline Venous FPG as covariate.	Baseline, 24 Weeks
Change From Baseline to Week 48 in Venous Fasting Plasma Glucose	Fasting Plasma glucose (FPG) is a test to determine how much glucose (sugar) is in a plasma sample after an overnight fast. Least Squares (LS) means was determined by ANCOVA model with LOCF and with terms for change from baseline in Venous FPG as response, treatment as fixed effect and baseline Venous FPG as covariate.	Baseline, 48 Weeks
Change From Baseline to Week 24 in Finger Stick Blood Glucose (FSBG)-Based Fasting Blood Glucose, Post Prandial Glucose	Fasting blood glucose (FBG) and post prandial glucose (PPG) [pre-breakfast (fasting) and post-breakfast (approximately 2 hours after breakfast)] was measured using FSBG. LS Mean was measured with ANCOVA model with LOCF and with terms for change from baseline in FSBG-based FBG/PPG as response, treatment as fixed effect and baseline FSBG-based FBG/PPG as covariate.	Baseline, 24 Weeks
Change From Baseline to Week 48 in Finger Stick Blood Glucose (FSBG)-Based Fasting Blood Glucose, Post Prandial Glucose	Fasting blood glucose (FBG) and post prandial glucose (PPG) [pre-breakfast (fasting) and post-breakfast (approximately 2 hours after breakfast)] was measured using FSBG. LS Mean was measured with ANCOVA model with LOCF and with terms for change from baseline in FSBG-based FBG/PPG as response, treatment as fixed effect and baseline FSBG-based FBG/PPG as covariate.	Baseline, 48 Weeks
Total Daily Insulin Dose at Week 24 and 48	Total daily insulin dose in the basal insulin analog and in Insulin Analog Mid Mixture group at week 24 and 48.	24 Weeks, 48 Weeks
Change From Baseline to Week 24 in Body Weight	LS means were calculated using ANCOVA model with LOCF and with terms for change from baseline in bodyweight as response, treatment as fixed effect and baseline bodyweight as covariate.	Baseline, 24 Weeks
Change From Baseline to Week 48 in Body Weight	LS means were calculated using ANCOVA model with LOCF and with terms for change from baseline in bodyweight as response, treatment as fixed effect and baseline bodyweight as covariate.	Baseline, 48 Weeks
Rate of Hypoglycemia at Week 24 and 48	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.	24 Weeks, 48 Weeks
Number of Participants With Insulin Treatment Change at Week 48	Insulin treatment change can be insulin treatment discontinuation, switch, intensification or reduction in frequency.; Discontinuation: Defined as stopping insulin treatment for 30 days or more.; Switch: Defined as stop the initial insulin therapy and started another insulin therapy of different class.; Intensification: Defined as any of the following: adding meal time insulin in basal insulin analog QD group; changing from BID to TID (Three times a day) in insulin analog mid mixture BID group; Reduction in frequency: Defined as any of the following: changing from BID to QD; changing from TID to BID or QD.	Baseline through 48 Weeks
Percentage of Participants Who Achieve the HbA1c <7% Without Switching and Discontinuing Study Insulin, and Without Using Rescue Therapy at Week 24	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Percentages of participants who achieved HbA1c levels of <7% were analyzed using a logistic regression model with logic link function, treatment as fixed effect and baseline HbA1c as continuous covariate.	24 Weeks
Percentage of Participants Who Achieve the HbA1c <7% Without Switching and Discontinuing Study Insulin, and Without Using Rescue Therapy at Week 48	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Percentages of participants who achieved HbA1c levels of <7% were analyzed using a logistic regression model with logic link function, treatment as fixed effect and baseline HbA1c as continuous covariate.	48 Weeks
Change From Baseline to Week 48 in Self-Efficacy About Insulin Therapy Questionnaire (SEITQ) Score	The SEITQ is designed to measure an individual's self-efficacy related to insulin therapy. The SEITQ consists of 5 items (that is, statements). The first 4 statements imply confidence in completing the tasks needed to take insulin correctly and avoid both hyperglycemia and hypoglycemia, whereas the last statement is an outcome expectation and implies that performance of these tasks will lead to avoidance of complications. Each item score ranges from 1 (strongly disagree) to 7 (strongly agree). The total SEITQ score is the sum of each item scores, with the range of 5 to 35. Higher SEITQ score indicates better outcome (higher self-efficacy). LS Mean was calculated using Mixed Models Analysis (MMRM) for repeated measures with all post-baseline SEITQ as responses, baseline SEITQ as a continuous covariate, treatment group, Visits, and treatment by visit interaction as fixed effects and participant as a random effect.	Baseline, 48 Weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Zeng T, Yuan H, Ren J, Li Y, Hou J, Du L, Zhu J, Chen L, Ji L. A Pragmatic Study of Basal and Mid-Mixture Insulins as Starter Insulins in Chinese Patients With Type 2 Diabetes: Observations From Long-Term, Real-World Experience. Diabetes Ther. 2021 Mar;12(3):931-941. doi: 10.1007/s13300-021-01007-z. Epub 2021 Feb 22.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2017
• Primary Completion (Actual): February 19, 2019
• Study Completion (Actual): July 12, 2019

Study Registration Dates

• First Submitted: January 11, 2017
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (Estimate): January 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 6, 2020
• Last Verified: August 15, 2019

More Information

Terms related to this study

• Keywords: mid mixture insulin analog; basal insulin analog
• 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
• Other Study ID Numbers: 16507; F3Z-GH-IOQR (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; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No