Empagliflozin as Adjunctive to inSulin thErapy in Type 1 diabetes over 52 weeks (EASE-2)

Phase 1

• Conditions: Type 1 diabetes mellitus; MedDRA version: 20.0Level: PTClassification code 10067584Term: Type 1 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2014-001922-14-FI
• Lead Sponsor: Boehringer Ingelheim Finland Ky

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05-05
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 720

Inclusion Criteria

1. Signed and dated written informed consent by the date of Visit 1 in accordance with
Good Clinical Practice (GCP) and local legislation

2. Male or female patient receiving insulin for the treatment of documented diagnosis of
T1DM for at least 1 year at the time of Visit 1

3. Fasting C-peptide value of < 0.7 ng/mL (0.23 nmol/L) at Visit 2 measured by the central
laboratory

4. Use of, and be willing, based on the Investigator’s judgement, to continue throughout the
duration of the trial, either:
- MDI of insulin consisting of at least one basal insulin injection and at least three daily
bolus injections OR
- CSII of any insulin type, with at least 5 months experience of using CSII prior to Visit 1

For both MDI and CSII, the total daily insulin dose must be = 0.3 U/kg and = 1.5 U/kg at
Visit 1

5. HbA1c = 7.5% and = 10.0% at Visit 5 measured by the central laboratory, and provided
that the patient’s HbA1c does not increase by > 0.5% between Visit 1 and Visit 5

6. Based on the Investigator’s judgement patient must have a good understanding of his/her
disease and how to manage it, and be willing and capable of performing the following
study assessments (assessed at Visits 1-5 and just before randomisation):
- patient-led management and adjustment of insulin therapy
- reliable approach to insulin dose adjustment for meals, such as carbohydrate counting
- reliable and regular home-based blood glucose monitoring
- recognise the symptoms of DKA, and reliably monitor for ketones
- implementation of an established sick day” management regimen

7. Age = 18 years at Visit 1

8. Body Mass Index (BMI) of = 18.5 kg/m2 at Visit 1

9. eGFR = 30 mL/min/1.73 m² as calculated by the CKD-EPI formula, based on creatinine
measured by the central laboratory at Visit 1

10. Women of child-bearing potential* 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. Such methods should be used throughout
the study and the patient must agree to periodic pregnancy testing during participation in
the trial. A list of contraceptive methods meeting these criteria will be provided in the
patient information

*Women of child-bearing potential are defined as follows:
Any female who has experienced menarche and is not post-menopausal (defined as at
least 12 months with no menses without an alternative medical cause) or who is not
permanently sterilised (e.g. hysterectomy, bilateral oophorectomy or bilateral
salpingectomy)

11. Compliance with trial medication administration must be between 80% and 120% during
the open-label placebo run-in period (see Section 4.1.8.1 for calculation of compliance),
to be judged before randomisation

Additional inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 576
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 144

Exclusion Criteria

1. History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or
chronic pancreatitis

2. Pancreas, pancreatic islet cells or renal transplant recipient

3. T1DM treatment with any other antihyperglycaemic drug (e.g. metformin, alphaglucosidase
inhibitors, glucagon-like-peptide 1 (GLP-1) analogues, SGLT-2 inhibitors,
pramlintide, inhaled insulin, pre-mixed insulins etc.) except subcutaneous basal and bolus
insulin within 3 months prior to Visit 1 or any history of clinically relevant
hypersensitivity according to Investigator’s judgement

4. Occurrence of severe hypoglycaemia involving coma/unconsciousness and/or seizure that
required hospitalisation or hypoglycaemia-related treatment by an emergency physician
or paramedic within 3 months prior to Visit 1 and until randomisation

5. Occurrence of DKA within 3 months prior to Visit 1 and until randomisation

6. Irregular sleep/wake cycle (e.g. patients who habitually sleep during the day and work
during the night) based on Investigator’s judgement

7. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or
transient ischaemic attack (TIA) within 3 months prior to Visit 1

8. Diagnosis of severe gastroparesis (based on Investigator’s judgement)

9. Diagnosis of brittle diabetes based on Investigator judgement

10. Indication of liver disease, defined by serum levels of either alanine transaminase (ALT),
aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal
(ULN) at Visit 1 or Visit 5 as measured by the central laboratory

11. Eating disorders such as bulimia or anorexia nervosa

12. Treatment with anti-obesity drugs, weight-loss surgery or aggressive diet regimen leading
to unstable body weight (based on Investigator’s judgement) 3 months prior to Visit 1
and until randomisation

13. Treatment with systemic corticosteroids or planned initiation of such therapy at Visit 1
and until randomisation. Inhaled or topical use of corticosteroids (e.g. for
asthma/chronic obstructive pulmonary disease) is acceptable

14. Change in dose of thyroid hormones within 6 weeks prior to Visit 1 or planned change or
initiation of such a therapy at Visit 1 and until randomisation

15. Patient is unwilling, based on the Investigator’s judgement, to avoid use of paracetamol
(acetaminophen) containing drugs throughout the CGM monitoring periods, since this
may falsely raise CGM glucose readings

16. Medical history of cancer or treatment for cancer in the last five years prior to Visit 1.
Resected basal cell carcinoma considered cured is exempted

17. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g.
malaria, babesiosis, haemolytic anaemia) at Visit 1

18. Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial

19. Alcohol or drug abuse within the 3 months prior to Visit 1 that would interfere with trial
participation based on Investigator’s judgement

20. Intake of an investigational drug in another trial within 30 days prior to Visit 1

21. Patient not able to understand and comply with study requirements, including the use of
an e-diary, based on Investigator’s judgement

22. Any other clinical condition that, based on Investigator’s judgement, would jeopardise
patient safety during trial participation or would affect the study outcome (e.g.
immunocompromised patients who might be at higher risk of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of empagliflozin in patients with T1DM as adjunctive to insulin therapy;Secondary Objective: To assess the safety and tolerability of empagliflozin in patients with T1DM as adjunctive to insulin therapy;Primary end point(s): 1: Change from baseline in HbA1c<br>;Timepoint(s) of evaluation of this end point: 1: 26 weeks<br>