E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of empagliflozin in patients with T1DM as adjunctive to insulin therapy |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of empagliflozin in patients with T1DM as adjunctive to insulin therapy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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
- Fasting C-peptide value of < 0.7 ng/mL (0.23 nmol/L) at Visit 2 measured by the central laboratory
- 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
- HbA1c >/= 7.5% and </= 10.0% at Visit 5 measured by the central laboratory
- Age >/= 18 years at Visit 1
Additional inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
- History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
- Pancreas, pancreatic islet cells or renal transplant recipient
- T1DM treatment with any other antihyperglycaemic drug (e.g. metformin, alpha-glucosidase inhibitors, 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
- Occurrence of severe hypoglycaemia involving coma and/or seizure that required hospitalisation or hypoglycaemia-related treatment by an emergency physician or paramedic within 3 months prior to Visit 1
- Occurence of severe DKA (i.e a pH of <7.0 or prolonged Intensive Care Unit admission exceeding two days) requiring hospitalisation within 3 months prior to Visit 1
Additional exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: Change from baseline in HbA1c
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1: Incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per patient-year
2: Incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per patient-year
3: Change from baseline in body weight
4: Change from baseline in total daily insulin dose (TDID)
5: Change from baseline in the percentage of time spent in target glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) as determined by continuous glucose monitoring (CGM)
6: Change from baseline in systolic blood pressure (SBP)
7: Change from baseline in diastolic blood pressure (DBP) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: week 5 to 26
2: week 1 to 26
3: 26 weeks
4: 26 weeks
5: weeks 23 to 26
6: 26 weeks
7: 26 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Netherlands |
Norway |
Poland |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 16 |