Efficacy and Safety Study of Empagliflozin as add-on to Insulin in Japanese Patients With Type 2 Diabetes Mellitus

A 52-week Randomised, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Empagliflozin Once Daily, as an add-on to Insulin in Japanese Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control

This is a multi-center, randomised, double-blind, placebo-controlled, parallel-group, efficacy and safety study of empagliflozin as add-on to insulin in Japanese patients with Type 2 Diabetes Mellitus with insufficient glycaemic control

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 269
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 456-0058
    • Nakayama Clinic
  • Chiba, Kashiwa, Japan, 277-0825
    • Kashiwa City Hospital
  • Fukuoka, Japan, 819-0168
    • Kunisaki Makoto Clinic
  • Fukuoka, Fukuoka, Japan, 810-0001
    • Saiseikai Fukuoka General Hospital
  • Fukuoka, Yanagawa, Japan, 832-0059
    • Seiwakai Medical Corporation Nagata Hospital
  • Gunma, Maebashi, Japan, 371-0821
    • Saiseikai Maebashi Hospital
  • Hiroshima, Fukuyama, Japan, 721-0927
    • Nippon Kokan Fukuyama Hospital
  • Hokkaido, Obihiro, Japan, 080-0016
    • Jiyugaoka Yokoyama Naika Clinic
  • Hokkaido, Obihiro, Japan, 080-0848
    • Jiyugaoka Yamada Clinic
  • Hokkaido, Sapporo, Japan, 060-0011
    • Souen Diabetes Clinic
  • Hyogo, Kobe, Japan, 657-0028
    • Kotani Diabetes Clinic
  • Hyogo, Nishinomiya, Japan, 663-8014
    • Nishinomiya Municipal Central Hospital
  • Ibaraki, Ushiku, Japan, 300-1207
    • Noritake Clinic
  • Kagawa, Japan, 761-8075
    • Yokoi Medical Clinic, Kagawa, I.M.
  • Kagoshima, Japan, 891-0401
    • Fukumoto clinic
  • Kagoshima, Kagoshima, Japan, 892-0824
    • Izuro Imamura Hospital
  • Kagoshima, Satsumasendai, Japan, 895-0052
    • Wakamatsu Memorial Hospital
  • Kanagawa, Atsugi, Japan, 243-0035
    • STOP DM SUZUKI DIABETES CLINIC, Kanagawa, I.M.
  • Kanagawa, Kamakura, Japan, 247-0056
    • Takai Naika Clinic
  • Kanagawa, Kawasaki, Japan, 210-0852
    • Kokan Clinic
  • Kyoto, Kyoto, Japan, 604-8151
    • Yoshimasa Diabetes & Endocrine Clinic
  • Kyoto, kyoto, Japan, 615-0035
    • Medical Corporation KEISEIKAI Kajiyama Clinic
  • Miyagi, Tagajo, Japan, 985-0835
    • Saka General Clinic
  • Nagano, Kitaazumi-gun, Japan, 399-8695
    • North Alps Medical Center Azumi Hospital
  • Nagano, Komoro, Japan, 384-8588
    • Asama Nanroku Komoro Medical Center
  • Oita, Oita, Japan, 870-0039
    • Abe Clinic
  • Okayama, Tsuyama, Japan, 708-0841
    • Tsuyama Chuo Hospital
  • Osaka, Japan, 530-0001
    • AMC Nishi-umeda Clinic
  • Osaka, Japan, 582-0005
    • Shiraiwa Medical Clinic
  • Osaka, Neyagawa, Japan, 572-8567
    • Medical Corporation Kyojinkai Clinic Komatsu
  • Osaka, Osaka, Japan, 559-0012
    • Minamiosaka Hospital
  • Osaka, Suita, Japan, 565-0853
    • OCROM Clinic
  • Saitama, Ageo, Japan, 362-8588
    • Ageo Central General Hospital
  • Saitama, Fujimi, Japan, 354-0031
    • Medical Corporation Kaishinkai Masunaga Clinic
  • Saitama, Saitama, Japan, 336-0963
    • Medical Corporation Fusa Shimizu Clinic Fusa
  • Tokyo, Adachi-ku, Japan, 123-0845
    • Seiwa Clinic
  • Tokyo, Bunkyo-ku, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Chiyoda-ku, Japan, 101-0024
    • Chiyoda Houjin Clinic
  • Tokyo, Chiyoda-ku, Japan, 102-0082
    • HDC Atlas Clinic
  • Tokyo, Chuo-ku, Japan, 103-0027
    • Fukuwa Clinic
  • Tokyo, Chuo-ku, Japan, 103-0027
    • Tokyo-Eki Center-building Clinic
  • Tokyo, Chuo-ku, Japan, 103-0028
    • Tokyo Center Clinic
  • Tokyo, Ota-ku, Japan, 144-0051
    • Shin Clinic
  • Tokyo, Shinjuku-ku, Japan, 169-0073
    • Shinjuku Research Park Clinic
  • Tokyo, Sumida-ku, Japan, 131-0046
    • Sumida Chuou Hospital
  • Yamagata, Sagae, Japan, 991-8508
    • Sagae City Hospital
  • Yamagata, Yamagata, Japan, 990-0885
    • Clinic Sugiyama
  • Yamanashi, Kofu, Japan, 400-8506
    • Yamanashi Prefectural Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Diagnosis of type 2 diabetes mellitus
• Patients on diet and exercise regimen who are pre-treated with any insulin therapy alone or in combination with 1 oral antidiabetic drug for at least 12 weeks prior to screening
• Fasting C-peptide must be > 0.5 ng/mL
• HbA1c at screening in Patients who are treated with insulin alone must be >=7.5% and <=10.0%
• HbA1c in Patients who are treated with insulin with 1 oral antidiabetic drug (OAD) must be >=7.0% and <=9.5% at screening, and >=7.5% and <=10.0% at placebo run-in period
• Age at informed consent must be >=20 and <75 years
• BMI at screening must be >22 and <=40 kg/m2
• Further inclusion criteria apply

Exclusion criteria:

• Patients who experience uncontrolled hyperglycaemia before randomization
• Patients who are treated with sulfonylurea whose dose is more than a half of daily maximum approval dose, glucagon-like peptide-1 (GLP-1) analogue, thiazolidinedione and sodium-glucose co-transporter 2 (SGLT-2) inhibitor
• Patients with recent cardiovascular and/or stroke events
• Patients with hepatic and/or renal dysfunction
• Patients who received anti-obesity drugs or other treatment leading to unstable body weight
• Patients who have known allergy or hypersensitivity to insulin and/or empagliflozin
• Pre-menopausal women who are nursing or pregnant
• Further exclusion criteria apply

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Placebo; Drug: Placebo; For blinding purposes
Experimental: empagliflozin 10 mg	Drug: Placebo; Drug: Empagliflozin; Drug: Placebo; For blinding purposes
Experimental: empagliflozin 25 mg	Drug: Placebo; Drug: Empagliflozin; Drug: Placebo; For blinding purposes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 16 Weeks of Treatment.	The primary endpoint was the change from baseline in HbA1c after 16 weeks of treatment. The term "baseline" refers to the last observation prior to the administration of any randomised study drug. Means presented are the adjusted means.	Baseline and 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Investigator Defined Drug-Related Adverse Events (AEs)	Percentage of patients with investigator defined drug-related Adverse Events (AEs) are presented	From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske SJ, Elsasser A, Ritter I, Steubl D, Wanner C, Wheeler DC. Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2015
• Primary Completion (Actual): April 18, 2017
• Study Completion (Actual): January 5, 2018

Study Registration Dates

• First Submitted: October 27, 2015
• First Submitted That Met QC Criteria: October 27, 2015
• First Posted (Estimate): October 28, 2015

Study Record Updates

• Last Update Posted (Actual): March 27, 2019
• Last Update Submitted That Met QC Criteria: December 11, 2018
• Last Verified: December 1, 2018

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: 1245.107

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No