A Study of Empagliflozin in Patients With Refractory Diabetes Mellitus With Insulin Resistance (EMPIRE-01)

A Multicenter, Open-label, Single-arm Study With Regard to the Efficacy and Safety of Empagliflozin in Patients With Refractory Diabetes Mellitus With Insulin Resistance

A multicenter, open-label, single-arm study with regard to the efficacy and safety of empagliflozin in patients with refractory diabetes mellitus with insulin resistance

Study Overview

• Status: Active, not recruiting
• Conditions: Insulin Resistance - Type A; Insulin Resistance - Type B; Lipoatrophic Diabetes Mellitus; Insulin Resistance Syndrome
• Intervention / Treatment: Drug: Empagliflozin Tablets

Detailed Description

To evaluate the clinical efficacy of a treatment with empagliflozin in refractory diabetes mellitus patients with insulin resistance (insulin resistance syndrome, lipoatrophic diabetes mellitus) by using the HbA1c change at Week 24 of treatment from baseline

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0017
      • Kobe University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329-0498
      • Jichi Medical University Hospital
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 101-8309
      • Nihon University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1) A patient who has been diagnosed with insulin resistance syndrome (type A, type B, type non-A non-B) or lipoatrophic diabetes mellitus prior to obtaining consent
• 2) A patient who has received consistent dosage and administration of drugs aiming a hypoglycemic effect and consistent instructions of diet therapy/exercise therapy for more than 12 weeks before enrollment
• 3) A patient with >= 7.0 % of HbA1c at the time of screening
• 4) A patient, if taking other SGLT2 inhibitor than empagliflozin, whose SGLT2 inhibitor can be washed out for more than 12 weeks prior to starting empagliflozin
• 5) A patient at the age of >=20 years at the time of consent
• 6) A patient who has received sufficient explanation with regard to information such as the objectives and details of this study, expected drug efficacy/pharmacological action, and risks, and has given written consent by her/himself.

Exclusion Criteria:

• 1) A patient with a medical history of acute coronary syndrome (including non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, and unstable angina pectoris), stroke or transient ischemic attack (TIA) within 3 months before obtaining consent
• 2) A patient with suspected hepatic dysfunction, that either of serum ALT, AST or alkaline phosphatase in the screening period is exceeding 3-fold of upper limit of normal rang
• 3) A patient who is receiving a systemic steroid at the time of consent (except for type B)
• 4) A patient whose thyroid hormone product dose has been changed within 6 weeks before obtaining consent
• 5) A patient with unstable endocrine diseases other than diabetes mellitus
• 6) A patient with hemolysis or blood diseases that destabilize erythrocytic cells and other various disorders (e.g., malaria, babesiosis, hemolytic anemia).
• 7) A premenopausal female patient (the latest menstruation was within 1 year before obtaining consent), a lactating or pregnant patient, or a patient who may be pregnant (without hysterectomy or ovariectomy) who has no intention to use efficacious contraception defined in this study during the treatment period and would not agree to receive regular pregnancy tests during the treatment period
• 8) A patient who has experienced alcohol abuse or drug abuse within 3 months before obtaining consent, which may disturb the study participation
• 9) A patient who is in the condition that makes it difficult to administer the study drug
• 10) A patient with renal dysfunction of eGFR (MDRD calculating formula) < 45 mL/min/1.73 m2 in the screening period
• 11) A patient who indicates a hypersensitivity response to empagliflozin or its excipients, or a patient with lactose-intolerance
• 12) A patient with severe ketosis, diabetic coma or precoma, severe infection, perioperative status, or serious trauma
• 13) A patient that the investigator and/or subinvestigator, etc., has judged to be ineligible to this study for other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment of empagliflozin; Empagliflozin 10 mg is to be continuously administered once daily for 12 weeks. Measure an HbA1c level after 12 weeks and determine the dose (Week 13 to Week 24). In case of <7.0%, 10 mg will be continued: in case of >=7.0%, it will be increased to 25 mg.	Drug: Empagliflozin Tablets; The administration is oral administration with water before or after breakfast.; Other Names: BI10773

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c change at Week 24 of the treatment from baseline	With regard to the HbA1c change at Week 24 of the treatment from baseline, changes will be shown by patient, as well as summarizing with the size of sample, mean, standard deviation, minimum, median, and maximum.	at Week 24 of the treatment from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c change rate at Week 24 of the treatment from baseline	With regard to the HbA1c change rate at Week 24 of the treatment from baseline, change rates will be shown by patient, as well as summarizing with the size of sample, mean, standard deviation, minimum, median, and maximum.	at Week 24 of the treatment from baseline
HbA1c change at Week 12 of the treatment from baseline	With regard to the HbA1c change at Week 12 of the treatment from baseline, changes will be shown by patient, as well as summarizing with the size of sample, mean, standard deviation, minimum, median, and maximum.	at Week 12 of the treatment from baseline
HbA1c over time	The HbA1c level at measurement time point is tabulated by patient, as well as plotting the HbA1c level over time by line graph. In addition, the mean, standard deviation, interquartile range, minimum, median, and maximum of HbA1c at each time point will be calculated and tabulated, as well as displaying the mean at each measurement time point with error bar of standard deviation by line graph.	at Week 24 of the treatment from baseline
Fasting plasma glucose (FPG) over time	The FPG level at measurement time point is tabulated by patient, as well as plotting the FPG level over time by line graph. In addition, the mean, standard deviation, interquartile range, minimum, median, and maximum of FPG at each time point will be calculated and tabulated, as well as displaying the mean at each measurement time point with error bar of standard deviation by line graph.	at Week 24 of the treatment from baseline
FPG change at Week 24 of the treatment from baseline	With regard to the FPG change at Week 24 of the treatment from baseline, changes will be shown by patient, as well as summarizing with the size of sample, mean, standard deviation, minimum, median, and maximum.	at Week 24 of the treatment from baseline
Change of insulin dose	The insulin dose of each patient will be tabulated by time point.	at Week 24 of the treatment from baseline
Postprandial glucose for 2 hours over time	The postprandial glucose for 2 hours at measurement time point is tabulated by patient, and the glucose level over time is plotted by line graph. In addition, the mean, standard deviation, interquartile range, minimum, median, and maximum of postprandial glucose for 2 hours at each time point will be tabulated, and the mean at each measurement time point with an error bar of standard deviation will be displayed by line graph.	2 Weeks from Day0 and Day140

Collaborators and Investigators

• Sponsor: Kobe University
• Collaborators: Boehringer Ingelheim
• Investigators: Study Chair: Wataru Ogawa, Kobe University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Anticipated): July 31, 2021
• Study Completion (Anticipated): October 30, 2021

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 3, 2021
• Last Update Submitted That Met QC Criteria: March 1, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: insulin resistance; refractory diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Skin Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Hyperinsulinism; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Skin Diseases, Metabolic; Diabetes Mellitus, Type 2; Lipodystrophy; Diabetes Mellitus; Metabolic Syndrome; Insulin Resistance; Lipodystrophy, Congenital Generalized; Diabetes Mellitus, Lipoatrophic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 190012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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