E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes with chronic kidney disease |
Type 2 diabetes med kronisk nyreinsufficiens |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes with chronic kidney disease |
Type 2 sukkersyge med varigt nedsat nyrefunktion |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045250 |
E.1.2 | Term | Type II diabetes mellitus with renal manifestations |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076408 |
E.1.2 | Term | Chronic kidney disease stage 1 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076410 |
E.1.2 | Term | Chronic kidney disease stage 3 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076411 |
E.1.2 | Term | Chronic kidney disease stage 4 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076409 |
E.1.2 | Term | Chronic kidney disease stage 2 |
E.1.2 | System Organ Class | 100000004857 |
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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 examine the effects of SGLT2-inhibition versus placebo on renal hemodynamics in patients with type 2 diabetes and chronic kidney disease |
At undersøge effekten af SLGT2-hæmning versus placebo på renal hæmodynamik hos patienter med type 2 diabetes og kronisk nyreinsufficiens |
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E.2.2 | Secondary objectives of the trial |
To examine the effects of SGLT2-inhibition versus placebo on systemic hemodynamics, water and sodium balance, tubular sodium transporters, vasoactive hormones and calcium-phosphate metabolism in patients with type 2 diabetes and chronic kidney disease |
At undersøge effekten af SLGT2-hæmning versus placebo på systemisk hæmodynamik, vand- og saltbalancen, tubulære natriumtransportere, vasoaktive hormoner og kalk-fosfat stofskiftet hos patienter med type 2 diabetes og kronisk nyreinsufficiens |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Over 18 years of age eGFR = 20-60 ml/min Type 2 diabetes diagnosed at least 1 year before inclusion and in stable antidiabetic Medical treatment for at least 3 months - HbA1c 48-70 mmol/mol - Fertile women are to use safe contraceptives |
- Alder: > 18 år - eGFR = 20-60 ml/min - Type 2 diabetes, diagnosticeret minimum 1 år inden inklusion og i stabil antidiabetisk medicinsk behandling i mindst 3 måneder - HbA1c 48-70 mmol/mol - Fertil kvinder skal anvende sikker antikonception gennem hele forsøgsperioden |
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E.4 | Principal exclusion criteria |
- Type 1 diabetes - Alcohol or substance abuse - Pregnancy or breast feeding - Anamnestic or clinical signs of heart or liver failure - Active cancers, aside from skin cancers (spinocellular or basocellular carinomas - BMI > 35 - Allgergies or unacceptable side effects to the experimental treatment or background treatment. - If investigator finds the participant unfit to complete the trial |
- Type 1 diabetes - Medicin- eller stofmisbrug - Alkoholoverforbrug - Graviditet eller amning - Aktive cancere, fraset hudcancere (spinocellulære og basocellulære carcinomer) - Anamnestiske eller kliniske tegn på betydende leversygdom eller hjertesvigt - Allergi for et af indholdsstofferne eller uacceptable bivirkninger til projektmedicin eller baggrundsmedicin. - BMI > 35 - Hvis deltageren efter investigators skøn ikke er egnet til at gennemføre projektet.
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E.5 End points |
E.5.1 | Primary end point(s) |
Renal Blood Flow |
Nyrernes blodgennemstrømning |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the trial, when all participants have completed the trial |
Ved forsøgets afslutning, når alle deltagere har afsluttet forsøget |
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E.5.2 | Secondary end point(s) |
1. GFR 2. Renal Vascular Resistance (RVF), Filtration Fraction (FF), Afferent and Efferent Renal Arteriolar Resistance (Ra and Re) 3. Systemic hemodynamics: Brachial blood pressure, central blood pressure, Heart rate, pulse wave velocity and arterial stiffness. 4. Water and sodium excretion: urinary sodium, Water clearance, urinary glucose, fractional sodium clearence, urinary excretion of tubular transporter proteins (AQP2, ENaC og NCC, NKCC), Extracellular Body Water (EBW), Total Body Water (TBW), Intracellular Body Water (IBW), Adipose Tissue Mass, Salt blood test 5. Plasma levels of vasoactive hormones ; renin, angiotensin II, aldosterone, vasopressin, BNP 6. The NO system measured by plasma and urinary levels of nitrate, nitrit, cGMP and pletysmography 7. HbA1C and blood glucose 8. Calcium-phosphate metabolism: PTH, phosphate, calcium, FGF23, alkalic phosphatase and urinary phosphate excretion 9. Beta-hydroxybutyrate and urate 10. urinary CL-K1 og CL-L1 11. Urinary Adenosin, NGAL, KIM-1 and IL-6
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1. GFR 2. Renal Vascular Resistance (RVF), Filtration Fraction (FF), Afferent og Efferent Renal Arteriolar Resistance (Ra og Re) 3. Systemisk hæmodynamik: Brachialt blodtryk, centralt blodtryk, hjertefrekvens, pulsbølgehastighed og karstivhed. 4. Vand- og saltudskillelse: urin-natrium, fritvandsclearence, urin-glucose, fraktionel natrium-udskillelse, urin-ekstretion af tubulære transportproteiner (AQP2, ENaC og NCC, NKCC), Extracellular Body Water (EBW), Total Body Water (TBW), Intracellular Body Water (IBW), Adipose Tissue Mass, salt blood test 5. Plasmaniveauer af vasoaktive hormoner med betydning for vand- og saltbalancen; renin, angiotensin II, aldosteron, vasopressin, BNP 6. NO-systemet vurderet ved plasma- og urinmålinger af nitat, nitrit og cGMP samt pletysmografi 7. Blodsukker: HbA1C og blodsukker 8. PTH, fosfat, calcium, FGF23, alkalisk fosfatase og urin fosfatudskillelse 9. Beta-hydroxybutyrat og urat 10. urinudskillelse af CL-K1 og CL-L1 11. Urin-udskillelse af Adenosin, NGAL, KIM-1 og IL-6
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of the trial, when all participants have completed the trial |
Ved forsøgets afslutning, når alle deltagere har gennemført forsøget |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | 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 | No |
E.8.1.6 | Cross over | Yes |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |