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 | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012613 |
E.1.2 | Term | Diabetes mellitus non-insulin-dependent |
E.1.2 | System Organ Class | 100000004861 |
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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 |
the effect of dapagliflozin on endothelial and microvascular function of the retinal circulation using Scanning-laser-Doppler-Flowmetry by assessing retinal capillary flow. |
Der Effekt von Dapagliflozin auf die endotheliale und mikrovaskuläre Funktion der retinalen Zirkulation anhand des retinalen kapillären Flusses mittels Scanning Laser Doppler Flowmetrie. |
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E.2.2 | Secondary objectives of the trial |
the effect of dapagliflozin on central (aortic) systolic pressure, central (aortic) pulse pressure and augmentation pressure, parameters that all are determined by pulse wave reflection (i.e. arterial wall properties) in the arterial tree.
the effect of retinal capillary flow after flicker light exposure (repeated flashes that cause vasodilatation by an in part NO dependent mechanism).
the effect of dapagliflozin on total body sodium content by 24 hour urinary sodium analysis and by using new MRI technology (at ISI of the University of Erlangen)
the effect of dapagliflozin on cardiovascular parameters, i.e. office blood pressure, fasting plasma glucose, postprandial glucose concentration and HbA1c
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Der Effekt von Dapagliflozin auf den zentralen systolischen Blutdruck, den zentralen Pulsdruck und den Augmentationsdruck mittels arterieller Pulswellenanalyse.
Der Effekt von Dapagliflozin auf den retinalkapillären Fluss nach Flickerlichtanwendung.
Der Effekt von Dapagliflozin auf den Gesamtkörpernatriumgehalt mittels 24 Stunden Urinnatriumessung und Na MRT.
Der Effekt von Dapagliflozin auf kardiovaskuläre Parameter wie Blutdruck, Nüchternglukose, postprandiale Blutgluosekonzentration und HbA1c |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Type 2 diabetes mellitus defined by fasting glucose ≥126 mg/dl or HbA1c ≥6.5% or on blood glucose lowering medication
Age of 18 - 75 years
Male and Female patients are eligible. Females of child bearing potential (WOCBP) are only eligible if pregnancy test at the screening visit is negative and they use adequate contraceptive precautions during the trial.
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Diabetes mellitus Typ 2, definiert als Nüchterglucosewert ≥126 mg/dl oder HbA1c ≥6.5% oder behandelter Diabetes mellitus
Alter 18-75 Jahre
Männer und Frauen (bei negativem Schwangerschaftstest bei der Screeningvisite und Kontrazeption während der Studiendauer) |
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E.4 | Principal exclusion criteria |
• age over 75 years
• Any other form of diabetes mellitus than type 2 diabetes mellitus
• History of diabetic ketoacidosis or hyperosmolar nonketotic coma
• Patients with more than one oral blood glucose lowering medication or on insulin therapy
• Any medication with loop diuretics
• Last measured HbA1c ≥ 10%
• Blood pressure levels ≥180/110 mmHg
• Estimated glomerular filtration rate (eGFR < 60 ml/min/1.73m²)
• Acute cardiovascular event (including myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, heart failure, stroke, TIA. PRIND, intracerebral bleeding) <3 months prior to screening visit (visit 0)
• Body mass index >40 kg/m²
• Triglyceride levels >1000 mg/dl
• HDL-cholesterol levels <25 mg/dl
• Macroalbuminuria defined by urinary albumine-to-creatinine ratio > 300 mg/g
• Known liver function test >3 times upper limit of normal
• Pregnant or breast-feeding patients
• Any patient currently receiving chronic (>30 consecutive days) treatment with an oral corticosteroid
• Subjects with a history of any serious hypersensitivity reaction to Dapagliflozin or SGLT-2 inhibitor
• Presence of significant renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, immunological, haematological or oncological, neurological and psychiatric diseases or dysfunction
• Diabetic retinopathy
• History of epilepsia or history of seizures
• Patients suffering from cataract or glaucoma
• History of drug medication abuse.
• Patients being treated for severe auto immune disease e.g. lupus
• Involvement in the planning and/or conduct of the study (applies to BMS or representative staff and/or staff at the study site)
• Participation in another clinical study within 30 days prior to visit -1
• Individuals at risk for poor protocol or medication compliance
• Subject who do not give written consent, that pseudonymous data will be transferred in line with the duty of documentation and the duty of notification according to § 12 and § 13 GCP-V
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
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Alter > 75 Jahre
andere Formen des Diabetes mellitus als Diabetes mellitus Typ 2
anamnestisch diabetische Ketoazidose oder hyperosmolares nichtketotisches Koma
mehr als ein Medikament zur Blutzuckersenkung oder Insulintherapie
Schleifendiuretika
zuletzt gemessener HbA1c ≥ 10%
Blutdruck ≥ 180/110 mmHg
eGFR < 60ml/min/1.73m²
akutes kardiovaskuläres Ereignis innerhalb der letzten 3 Monate vor der Screeningvisite (Myokardinfarkt, instabile Angina pectoris, PTA, Herzinsuffizienz, Apoplex, TIA, PRIND, intracerebrale Blutung)
BMI > 40kg/m²
Hypertriglycerinämie >1000mg/dl
HDL Choleserinämie < 25mg/dl
Makroalbuminurie (Albumin Kreatininratio > 300mg/g)
erhöhte Leberwerte (über 3fach erhöht)
schwangere oder stillende Frauen
Patienten mit vorrübergehender oder chronischer Behandlung (> 30 aufeinanderfolgenden Tagen) mit Glukokortikoiden
bekannte Allergie gegen Dapagliflozin oder andere SGLT 2 Inhibitoren
bekannte signifikante renale, respiratorische, hepatische, gastrointestinale, endokrine oder metabolische, immunologische, hämatologische oder onkologische, neurologische oder psychatrische Erkrankungen
diabetische Retinopathie
bekannte Epilepsie oder Anfallsleiden
Patienten mit Katarakt oder Glaukom
bekannte Medikamentenabusus
bekannte behandelte Autoimmunerkrankung, z.B. Lupus
Patienten, die an der Planung oder Durchführung der Studie beteiligt sind
Patienten, die anderen Studien innerhalb der letzten 30 Tage vor der Screeningvisite teilgenommen haben
Patienten mit mangelnder Compliance
Patienten, die keine Einverständniserklärung abgegeben haben
Gefänginsinsassen
Patienten welche aufgrund einer psychatrischen oder somatischen Erkrankung (z.B. Infektionserkrankung) nicht teilnehmen können
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E.5 End points |
E.5.1 | Primary end point(s) |
The effect of dapagliflozin on endothelial and microvascular function of the retinal circulation using Scanning-laser-Doppler-Flowmetry by assessing the retinal capillary flow |
Der Effekt von Dapagliflozin auf die endotheliale und mikrovaskuläre Funktion der retinalen Zirkulation anhand des retinalen kapillären Flusses mittels Scanning Laser Doppler Flowmetrie. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after second phase of crossoverdesign |
nach der zweiten Phase von 4 Wochen im Crossoverdesign |
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E.5.2 | Secondary end point(s) |
on central (aortic) systolic pressure, central (aortic) pulse pressure and augmentation pressure, parameters that all are determined by pulse wave reflection (i.e. arterial wall properties) in the arterial tree.
on retinal capillary flow after flicker light exposure (repeated flashes that cause vasodilatation by an in part NO dependent mechanism).
on total body sodium content by 24 hour urinary sodium analysis and by using new MRI technology (at imaging science institute of the University of Erlangen)
on cardiovascular parameters, i.e. office blood pressure, fasting plasma glucose, postprandial glucose concentration and HbA1c
|
Der Effekt von Dapagliflozin auf den zentralen systolischen Blutdruck, den zentralen Pulsdruck und den Augmentationsdruck mittels arterieller Pulswellenanalyse.
Der Effekt von Dapagliflozin auf den retinalkapillären Fluss nach Flickerlichtanwendung.
Der Effekt von Dapagliflozin auf den Gesamtkörpernatriumgehalt mittels 24 Stunden Urinnatriumessung und Na MRT.
Der Effekt von Dapagliflozin auf kardiovaskuläre Parameter wie Blutdruck, Nüchternglukose, postprandiale Blutgluosekonzentration und HbA1c |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after second phase of crossoverdesign |
nach der zweiten Phase von 4 Wochen im Crossoverdesign |
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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 | 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 | 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 | 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 | 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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LSLV |
letze Visite des letzten Patienten |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |