E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-Transplant Diabetes Mellitus |
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E.1.1.1 | Medical condition in easily understood language |
Hyperglycemia needing medical treatment after kidney transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
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 whether monotherapy with empagliflozin has the same efficacy in controlling hyperglycaemia as standard basal insulin therapy (not succeeding 40 IE/day) in kidney transplanted patients with PTDM, as judged by 2-hour glucose levels during an oral glucose tolerance test (OGTT).
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E.2.2 | Secondary objectives of the trial |
To assess differences in the change of HbA1c after 3 months of empagliflozin monotherapy compared to baseline HbA1c. To assess the efficacy of empagliflozin, judged by differences in glycaemic control (glucose profiles and urinary glucose) after 1 month of empagliflozin monotherapy compared to baseline glycaemic control. To assess differences in metabolic parameters (insulin secretion and insulin sensitivity after 1 month of empagliflozin monotherapy compared to baseline insulin secretion and sensitivity). To assess the safety of empagliflozin in kidney transplanted patients, and specifically whether monotherapy with empagliflozin can be upheld for at least 1 year without clinically intolerable side effects (ketoacidosis, urinary tract infections, genital infections, decline of renal function, rate of bone fractures) according to best clinical care standard. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosed PTDM defined as: 2 hour plasma glucose level ≥ 200 mg/dL in the OGTT (75mg glucose), twice blood glucose levels ≥ 200 mg/dL during random controls or twice fasting glucose levels ≥ 125 mg/dL or HbA1c ≥ 6.5% Stable graft function for more than 6 months post transplantation (eGFR ≥ 30 ml/min) At least 6 months of basal insulin therapy for PTDM |
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E.4 | Principal exclusion criteria |
Age< 18 years Patients with prior history of type 1 or type 2 diabetes Pregnancy Severe renal impairment (GFR < 30 mL/min./1.73 m2) Severe blood glucose elevation with the need for therapy with insulin > 40 IE/day or HbA1c >8.5%. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline blood glucose levels of the 2h value after OGTT (75g glucose) after 1 month of empagliflozin monotherapy. Maximum tolerable change from baseline blood glucose levels should not exceed > 20 mg/dL on average (>100 mg/dL in each individual). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 month after start of treatment |
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E.5.2 | Secondary end point(s) |
Mean change from baseline insulin secretory capacity and insulin sensitivity after 1 month of empagliflozin monotherapy (derived by OGTT). Mean change from baseline HbA1c serum levels after 3 month of empagliflozin monotherapy. Mean change from baseline body weight after 1 month of empagliflozin monotherapy. Mean change from baseline blood pressure after 1 month of empagliflozin monotherapy. No clinically intolerable ketoacidosis or ketonuria after 1 month of empagliflozin monotherapy. No clinically intolerable urinary tract infections (UTI) after 1 month of empagliflozin monotherapy. No decline of renal function defined by eGFR of <25% after 1 month of empagliflozin monotherapy. Mean change from baseline blood glucose levels of the 2h value after OGTT (75g glucose) during the entire study period of 1 year of empagliflozin monotherapy. If changes from baseline blood glucose levels exceed >50 mg/dL on average (>100 mg/dL in each individual), patients will receive add-on insulin therapy. Mean change from baseline insulin secretory capacity and insulin sensitivity during the entire study period of 1 year of empagliflozin monotherapy. (OGTT). Mean change from baseline HbA1c serum levels from baseline during the entire study period of 1 year of empagliflozin monotherapy. Mean change from baseline body weight from baseline during the entire study period of 1 year of empagliflozin monotherapy. Mean change from baseline blood pressure from baseline during the entire study period of 1 year of empagliflozin monotherapy. No clinically intolerable ketoacidosis (determined by venous blood gas analysis) or ketonuria (determined by blood and urinary analysis) during the entire study period of at least 1 year of empagliflozin monotherapy. No clinically intolerable of urinary tract infections (UTI) or genital infections during the entire study period of 1 year of empagliflozin monotherapy. No decline of renal function defined by eGFR of >25% during the entire study period of 1 year of empagliflozin monotherapy. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 month and 1 year after start of treatment |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |