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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04233801
• Other study ID #: 1245-0191
• Status: Completed
• Phase: Phase 3
• Start date: April 15, 2020
• Est. completion date: March 10, 2022

Study information

• Verified date: March 2023
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 219
• Est. completion date: March 10, 2022
• Est. primary completion date: March 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Empagliflozin
Empagliflozin
• Placebo
Placebo

Locations

Country	Name	City	State
China	Beijing Pinggu Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	The Second Hospital of Jilin University	Changchun
China	The third xiangya hospital of Central South University	Changsha
China	Chongqing Three Gorges Central Hospital	Chongqing
China	The First Hospital, Chongqing Medical University	Chongqing
China	Third Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	The Affiliated Hospital of Hangzhou Normal University	Hangzhou
China	The Second Affiliated Hospital of Nanjing Medical University	Hangzhou
China	Anhui Provincial Hospital	Hefei
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang
China	Jiangxi Provincial People's Hospital	Nanchang
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	The Second Affiliated Hospital to Nanchang University	Nanchang
China	The affiliated hospital of medicalcollege qingdao university	Qingdao
China	Centre Hospital of Putuo District, Shanghai	Shanghai
China	Shanghai Fifth People's Hospital affiliated to Fudan University	Shanghai
China	Tongren hospital, Shanghai Jiaotong University School of Medicine	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang
China	Suzhou Municipal Hospital	Suzhou
China	The First Affiliated Hospital of Soochow University	Suzhou
China	Tianjin Medical University Chu Hisen-I Memorial Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.

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