Regulatory Request NIS in Korea

A Regulatory Requirement Non Interventional Study to Monitor the Safety and Effectiveness of JARDIANCE DUO® (Empagliflozin/Metformin, 5/500mg, 5/850mg, 5/1000mg, 12.5/500mg, 12.5/850mg, 12.5/1000mg) in Korean Patients With Type 2 Diabetes Mellitus

To monitor the safety profile and effectiveness of JARDIANCE DUO® in Korean patients with type 2 diabetes mellitus in a routine clinical practice setting

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: JARDIANCE DUO®

• Study Type: Observational
• Enrollment (Actual): 658

Contacts and Locations

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of, 15355
    • Korea University Ansan Hospital
  • Bucheon, Korea, Republic of, 14754
    • Hyewon Medical Foundation Sejong Hospital
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Hospital
  • Daejeon, Korea, Republic of, 35233
    • Eulji University Hospital
  • Goyang, Korea, Republic of, 10475
    • Myongji Hospital
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital
  • Seongnam, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 02447
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacred Heart Hospital
  • Seoul, Korea, Republic of, 04763
    • Hanyang University Seoul Hospital
  • Seoul, Korea, Republic of, 02053
    • Seoul Medical Center
  • Seoul, Korea, Republic of, 01757
    • Inje University Sanggye Paik Hospital
  • Seoul, Korea, Republic of, 04404
    • SoonChunHyang University Seoul Hospital
  • Seoul, Korea, Republic of, 07937
    • Hongik Hospital
  • Suwon, Korea, Republic of, 16499
    • Ajou University Hospital
  • Wonju, Korea, Republic of, 26426
    • Yonsei University Wonju Severance Christian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is an observational prospective, non-interventional, open-label, multi-centre national study. It will provide additional safety information of JARDIANCE DUO® (empagliflozin/metformin) in Korean patients with type 2 diabetes mellitus in a routine clinical practice setting

Description

Inclusion Criteria:

• Patients who have started at first time on JARDIANCE DUO® in accordance with the approved label in Korea
• Age ≥19 years at enrolment
• Patients who have signed on the data release consent form

Exclusion Criteria:

• Patients with previous exposure to JARDIANCE®, JARDIANCE DUO®
• Hypersensitivity to active ingredients empagliflozin and/or metformin or to any of the excipients
• Moderate (stage 3b) and severe renal failure (CrCl < 45 ml/min or eGFR < 45 ml/min/1.73 square meter)
• Acute conditions with the potential to alter renal function such as: dehydration, severe infection, cardiovascular collapse (shock), acute myocardial infarction, sepsis
• Type1 diabetes, acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma, history of a ketoacidosis (type 1 diabetes and diabetic ketoacidosis should be treated with insulin).
• Congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure
• Radiologic studies involving the use of intravascular iodinated contrast materials (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials)
• Intravascular administration of iodinated contrast media may lead to acute renal failure and has been associated with lactic acidosis in patients receiving metformin.

Therefore, in patients with eGFR > 60ml/min/1.73m2, JARDIANCE DUO® must be discontinued prior to, or at the time of the test and not be reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and has not deteriorated further. In patients with moderate renal impairment (eGFR 45-60 ml/min/1.73m2), JARDIANCE DUO® must be discontinued 48 hours before administration of iodinated contrast media and not be reinstituted until at least 48 hours afterwards, and only after renal function has been re-evaluated and has not deteriorated further.

• In patients with severe infections or severe traumatic systemic disorders, JARDIANCE DUO® should be temporarily suspended, and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal.
• JARDIANCE DUO® should be temporarily suspended for any surgical procedure(except minor procedures not associated with restricted intake of food and fluids)before 48 hours, and not be reinstituted until 48 hours afterwards, after renal function has been evaluated as normal.
• Patients with malnutrition, starvation, hypostheniam pituitary or adrenal insufficiency
• Impaired hepatic function (since impaired hepatic function has been associated with some cases of lactic acidosis, JARDIANCE DUO® should generally be avoided in patients with clinical or laboratory evidence of hepatic disease), pulmonary infarction, severe respiratory impairment, any condition associated with hypoxemia, excessive alcohol intake, GI disorders such as dehydration, diarrhoea or vomiting
• Pregnant women, women who may be pregnant, nursing women
• Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic disease) such as: decompensated heart failure, respiratory failure, recent myocardial infarction, shock
• Current participation in other clinical trials

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects diagnosed with type 2 diabetes mellitus	Drug: JARDIANCE DUO®; empagliflozin and metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Any Adverse Events	Percentage of participants with any adverse events was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.	From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Percentage of Participants With Adverse Events Relating to Study Drug	Percentage of participants with adverse events relating to study drug was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.	From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Percentage of Participants With Unexpected Adverse Events	Percentage of participants with unexpected adverse events was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.	From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Percentage of Participants With Adverse Events of Special Interest	Percentage of participants with adverse events of special interest was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.	From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Percentage of Participants With Adverse Events Leading to Discontinuation of the Drug	Percentage of participants with adverse events leading to discontinuation of the drug was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.	From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Glycosylated Hemoglobin (HbA1c) at Last Visit From Baseline	Change in the glycosylated hemoglobin (HbA1c) at Last Visit from baseline was reported.	At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Number of Participants Reached Target Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c < 7%) at Last Visit	Number of participants reached target effectiveness response in the glycosylated hemoglobin (HbA1c) (HbA1c < 7%) at Last Visit was reported. Target effectiveness response in the glycosylated hemoglobin (HbA1c) was defined as HbA1c less than 7%.	At last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Number of Participants With Relative Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c Decrease of 0.5% Comparing to Baseline) at Last Visit	Number of participants with relative effectiveness response in the glycosylated hemoglobin (HbA1c) at Last Visit was reported. Relative effectiveness response in the glycosylated hemoglobin (HbA1c) at last visit was defined as HbA1c decrease of 0.5% or more at the last visit comparing to baseline.	At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Change in the Fasting Plasma Glucose (FPG) at Last Visit From Baseline	Change in the Fasting Plasma Glucose (FPG) at Last Visit from baseline was reported.	At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Change in the Body Weight at Last Visit From Baseline	Change in the body weight at Last Visit from baseline was reported.	At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Change in the Systolic Blood Pressure (SBP) at Last Visit From Baseline	Change in the systolic blood pressure (SBP) at Last Visit from baseline was reported.	At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Change in the Diastolic Blood Pressure (DBP) at Last Visit From Baseline	Change in the diastolic blood pressure (DBP) at Last Visit from baseline was reported.	At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Number of Participants Per Final Effectiveness Assessment Category at Last Visit	Number of participants per final effectiveness assessment category at Last Visit was reported. The final effectiveness consisted of 4 categories: Improved (If determined as there was any effect of maintaining or improving disease related factors.), Unchanged (If disease related factors had not been changed compared with before administration, and not determined as there was any effect of maintaining symptoms.), Aggravated (If disease related factors were worse than before administration.), and Unassessable (If it cannot be determined due to insufficient information collected.).	At last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Jane(JiEun) Lee, 8227090092, jane.lee.ext@boehringer-ingelheim.com

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2018
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 21, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): May 21, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

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: 1276-0039

Plan for Individual participant data (IPD)

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

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). Requestors can use the following link http://trials.boehringer-ingelheim.com/ to:

1. find information in order to request access to clinical study data, for listed studies.
2. request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement.

Drug and device information, study documents

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