A Study to Test How Well Empagliflozin Works in Chinese Patients With Type 2 Diabetes Who Already Take Insulin

A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group Study of Empagliflozin (10 mg and 25 mg) Administered Orally Once Daily in Combination With Insulin With or Without up to Two Oral Anti-diabetic Agents for 24 Weeks in Chinese Type 2 Diabetic Patients With Insufficient Glycemic Control.

This is a study in Chinese adults with type 2 diabetes. The study is open to people who take insulin but still have too high blood sugar levels. Participants may additionally be taking up to 2 other medicines for their diabetes. The purpose of this study is to find out whether empagliflozin taken together with insulin helps people with type 2 diabetes to better control their blood sugar.

The participants are in the study for about 7 months. During this time, they visit the study site about 8 times, 1 additional visit may be either a visit to the study site or a phone call. At the start of the study, participants are put into 3 groups by chance. Participants get either 10 mg empagliflozin tablets, or 25 mg empagliflozin tablets, or placebo tablets once a day. Placebo tablets look like empagliflozin tablets but do not contain any medicine.

The doctors regularly take blood samples from the participants. The changes in blood sugar levels are compared between the groups. The doctors also check the general health of the participants.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Empagliflozin

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 101200
    • Beijing Pinggu Hospital
  • Changchun, China, 130041
    • The Second Hospital of Jilin University
  • Changsha, China, 410013
    • The Third Xiangya Hospital of Central South University
  • Chongqing, China, 400042
    • The First Hospital, Chongqing Medical University
  • Chongqing, China, 404000
    • Chongqing Three Gorges Central Hospital
  • Guangzhou, China, 510150
    • Third Affiliated Hospital of Guangzhou Medical University
  • Hangzhou, China, 310015
    • The Affiliated Hospital of Hangzhou Normal University
  • Hangzhou, China, 210011
    • The Second Affiliated Hospital of Nanjing Medical University
  • Hefei, China, 230001
    • Anhui Provincial Hospital
  • Luoyang, China, 471000
    • The First Affiliated Hospital of Henan University of Science and Technology
  • Nanchang, China, 330006
    • The Second Affiliated Hospital to Nanchang University
  • Nanchang, China, 330006
    • The First Affiliated Hospital of Nanchang University
  • Nanchang, China, 330006
    • Jiangxi Provincial People's Hospital
  • Qingdao, China, 266005
    • The affiliated hospital of medicalcollege qingdao university
  • Shanghai, China, 200240
    • Shanghai Fifth People's Hospital affiliated to Fudan University
  • Shanghai, China, 200062
    • Centre Hospital of Putuo District, Shanghai
  • Shanghai, China, 200051
    • Tongren hospital, Shanghai Jiaotong University School of Medicine
  • Shenyang, China, 110072
    • Shengjing Hospital of China Medical University
  • Suzhou, China, 215006
    • The First Affiliated Hospital of Soochow University
  • Suzhou, China, 215002
    • Suzhou Municipal Hospital
  • Tianjin, China, 300070
    • Tianjin Medical University Chu Hisen-I Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years and ≤75 years old at Visit 1;
• Chinese patient with diagnosis of Type 2 diabetes prior to Visit 1;

• A stable treatment with premixed Insulin (≥ 20IU/day) or basal insulin (≥ 16 IU/day) for at least 12 weeks prior to enrolment with or without up to two OADs

  • With maximum insulin dose of ≤ 1 unit/kg/day. Acceptable basal insulins should have duration of action up to 24 h such as insulin Degludec, insulin glargin, insulin detemir or NPH (neutral protamine hagedorn) insulin; Acceptable pre-mixed insulins could be once or twice daily posology only. The total insulin dose should not be changed by more than 20% of the baseline value within the 12 weeks prior to randomisation (Visit 3). Both human insulin & insulin analogue are acceptable;
  • If the patient is taking OADs, regimen has to be unchanged for at least 12 weeks prior to randomization (Visit 3);
  • If the patient is taking metformin, stable dose (at least 1500 mg daily or maximum tolerated dose) must be maintained for at least 12 weeks without dose adjustments prior to randomization (Visit 3);
• HbA1c ≥7.5% and ≤11.0% at Visit 1;
• Fasting C-peptide: >0.5 ng/mL (>166pmol/L) at Visit 1；
• 18.5 kg/m2 ≤ BMI ≤ 45 kg/m2 at Visit 1;
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial;
• Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

Exclusion Criteria:

• Diagnosis of Type 1 diabetes;
• Patients receiving MDI insulin or insulin pump treatment;
• eGFR <45ml/min/1.73m2 calculated based on MDRD formula;
• Uncontrolled hyperglycemia [glucose level >13. 9 mmol/l after an overnight fast during placebo run-in];
• Severe hypoglycemia episode (event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions) within 6 months prior to Visit 1;
• History of diabetic ketoacidosis or hyperosmolar non-ketotic coma. Myocardial infarction, stroke or transient ischaemic attack within 3 months prior to Visit 1;
• Bariatric surgery;
• Further criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin 10 mg; 1 table of 10 milligrams (mg) of Empagliflozin was administered orally once daily for a treatment period of 24 weeks. Before the first dose of randomised drug, all participants went through a 2-week open label placebo run-in period, taking Placebo tablets orally once daily.	Drug: Empagliflozin; Empagliflozin
Experimental: Empagliflozin 25 mg; 1 table of 25 milligrams (mg) of Empagliflozin was administered orally once daily for a treatment period of 24 weeks. Before the first dose of randomised drug, all participants went through a 2-week open label placebo run-in period, taking Placebo tablets orally once daily.	Drug: Empagliflozin; Empagliflozin
Placebo Comparator: Placebo; Matching placebo was administered orally once daily for a treatment period of 24 weeks. Before the first dose of randomised drug, all participants went through a 2-week open label placebo run-in period, taking Placebo tablets orally once daily.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) at Week 24	A restricted maximum likelihood (REML) based mixed model repeated measures (MMRM) approach was applied including treatment, background therapy, and visit as fixed classification effects, baseline HbA1c and baseline estimated glomerular filtration rate (eGFR) as the linear covariates, treatment by visit interaction, and baseline HbA1c by visit interaction.	At baseline (Week 0) and at Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HbA1c<7.0% at Week 24	Percentage of participants with glycosylated haemoglobin A1c (HbA1c) <7.0% at Week 24 is reported.	At Week 24
Change in Body Weight From Baseline to Week 24	Change in body weight from baseline to Week 24 is reported. A restricted maximum likelihood (REML) based mixed model repeated measures (MMRM) approach was applied including baseline body weight, and its interaction with visit.	At baseline (Week 0) and at Week 24
Change From Baseline in Systolic Blood Pressure (SBP) at Week 24	A restricted maximum likelihood (REML) based mixed model repeated measures (MMRM) approach was applied including baseline SBP and its interaction with visit.	At baseline (Week 0) and at Week 24
Change From Baseline in Diastolic Blood Pressure (DBP) at Week 24	A restricted maximum likelihood (REML) based mixed model repeated measures (MMRM) approach was applied including baseline DBP and its interaction with visit.	At baseline (Week 0) and at Week 24
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	A restricted maximum likelihood (REML) based mixed model repeated measures (MMRM) approach was applied including baseline FPG and its interaction with visit.	At baseline (Week 0) and at Week 24
Change From Baseline in 2-hour Post-prandial Glucose (PPG) at Week 24	The Analysis of covariance (ANCOVA) model included treatment and background therapy as classification effects, baseline PPG and baseline Estimated glomerular filtration rate (eGFR) as the linear covariates.	At baseline (Week 0) and at Week 24
Number of Participants With Confirmed Hypoglycaemic Events	Confirmed hypoglycemic events refer to the hypoglycaemic events with a plasma glucose value of ≤70 milligrams per deciliter (mg/dL) or where assistance was required.	From first administration of the initial randomised study medication to last intake of study medication + 7 days (inclusive), up to 176 days.
Number of Participants With Adjudicated Diabetic Ketoacidosis (DKA) Events	The risk of DKA had to be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty in breathing, confusion, unusual fatigue or sleepiness. In case of a suspected DKA, the investigator was to ensure that appropriate tests were performed at the earliest opportunity according to 2017 China Type 2 diabetes mellitus (T2DM) guidelines. An independent external Clinical event committee (CEC) was established to adjudicate centrally and in a blinded fashion events suspected of DKA and certain hepatic events. DKA was investigated using both broad and narrow Boehringer Ingelheim customised MedDRA query (BIcMQs).	From first administration of the initial randomised study medication to last intake of study medication + 7 days (inclusive), up to 176 days.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Actual): March 3, 2022
• Study Completion (Actual): March 10, 2022

Study Registration Dates

• First Submitted: January 16, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

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; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 1245-0191

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of 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