Empagliflozin and ACEi- Effects on Hyperfiltration: BETWEEN Study

Study Overview
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Brief Summary
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This is a randomized, double-blind, double-dummy, placebo-controlled, cross over design trial with empagliflozin compared to placebo that is added to open-label ramipril.

Official Title
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A Double-blind, Placebo Controlled, Cross-over Renal Mechanistic Trial to Assess the Effect of Adding Empagliflozin Versus Placebo on Renal Hyperfiltration on a Background of the Angiotensin Converting Enzyme Inhibitor (ACEi) Ramipril: BETWEEN Study

Conditions
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Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Obesity

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Placebo (matching empagliflozin)
* Drug: ramipril


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed and dated written informed consent. Male or female patients diagnosed with type 1 diabetes (T1D) at least 6 months prior to informed consent or type 2 diabetes (T2D) or non-diabetic obese patients. T1D patients must use and be willing of and be willing to continue throughout the duration of the trial either: multiple daily injections of insulin OR continuous sub-cutaneous insulin infusion of any insulin type, with at least 3 months experience For patients with T1D or T2D,HbA1c of 6.5 - 11% Age at least 18 years of age Body mass index of >=18.5 kg/m^2 Estimated glomerular filtration rate greater than or equal to 60 ml/min/1.73m2 Blood pressure greater than 90 /60 mmHg and less than or equal to 140 / 90 mmHg Use of a highly effective method of contraception. Further inclusion criteria apply Exclusion criteria: For patients with T1D, treatment with an antihyperglycaemic agent within 3 months prior to visit 1 occurrence of severe hypoglycaemia within 3 months prior to visit 1 hypoglycaemic unawareness within 3 months prior to visit 1 occurrence of diabetic ketoacidosis within 3 months of visit 1 and until visit 3 Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A<br>Empagliflozin followed by a wash-out followed by empagliflozin matching placebo on a background of open label ramipril. | Drug: Empagliflozin<br>* Empagliflozin will be taken once daily<br>Drug: Placebo (matching empagliflozin)<br>* Placebo will be taken once daily<br>Drug: ramipril<br>* Ramipril will be taken once or twice daily<br>|
| Experimental: Sequence B<br>Empagliflozin matching placebo followed a wash-out followed by empagliflozin on a background of open label ramipril. | Drug: Empagliflozin<br>* Empagliflozin will be taken once daily<br>Drug: Placebo (matching empagliflozin)<br>* Placebo will be taken once daily<br>Drug: ramipril<br>* Ramipril will be taken once or twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular Filtration Rate (GFR) Under Euglycaemic Conditions After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril. | Glomerular filtration rate (GFR) under euglycaemic conditions after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers. | At week 4 and at week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Filtration Status (Glomerular Filtration Rate (GFR) < 120 mL/Min/1.73m², Yes/no) After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril | Filtration status (Glomerular Filtration Rate (GFR) < 120 mL/min/1.73m²) after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. Filtration status is defined as whether a patient has normal Filtration status (GFR < mL/min/1.73m², yes) or not (GFR ≥ mL/min/1.73m², no). The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers. | At week 4 and at week 12. |