E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Linagliptin in Patients with Hypertension and Albuminuria |
Linagliptin bei Patienten mit Bluthochdruck und Albuminurie |
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E.1.1.1 | Medical condition in easily understood language |
Hypertension and Albuminuria |
arterieller Bluthochdruck und Albuminurie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038464 |
E.1.2 | Term | Renal hypertension |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001580 |
E.1.2 | Term | Albuminuria |
E.1.2 | System Organ Class | 10038359 - Renal and urinary 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 |
The objective of this study is to investigate the effect of Linagliptin in comparison to placebo on the urine albumin-to-creatinine ratio (UACR) in patients with high blood pressure and an increased albumin excretion. |
Das Ziel dieser Studie besteht in der Erforschung der Wirkung von Linapliptinim Vergleich mit Placebo auf das Albumin-Kreatin-Verhältnis im Urin bei Patienten mit Bluthochdruck und erhöhter Albuminausscheidung |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patient has signed and dated written informed consent to participate in the trial 2.Arterial hypertension 3.Stable antihypertensive treatment within the last 3 months 4.Age ≥ 45 – ≤ 80 years 5.Micro- or macroalbuminuria defined as UACR in morning urine > 20 mg/g in female and > 30 mg/g in male and/or arterial hypertension for more than 5 years currently treated with two or more antihypertensive drugs to control blood pressure and a history of cardiovascular disease or stroke. 6.Patient consents that his/her family physician will be informed of trial participation
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1. Unterschriebene Patienteninformation/Einwilligungserklärung 2. Arterieller Bluthochdruck 3. Stabile Bluthochdrucktherapie innerhalb der letzten 3 Monate 4. Alter: ≥45 bis ≤80 Jahre 5. Mikro- oder Makroalbuminurie (Morgen-UACR >20 mg/g bei Frauen bzw. >30mg/g bei Männern) und/ oder arterieller Bluthochdruck seit mehr als 5 Jahren behandelt mit 2 oder mehr Antihpertensiva zur Bluthochdruckontrolle sowie eine Vorgeschichte Kardiovaskulärer Erkrankungen oder Schlaganfall. 6. Einwilligung zur Information des Hausarztes.
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E.4 | Principal exclusion criteria |
1.History of type 1 diabetes 2.History of type 2 diabetes 3.Uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg) 4.Acute infections 5.Any history of glomerulonephritis 6.Any kidney disease not caused by hypertension as judged by the Investigator 7.Glomerular filtration rate (GFR) < 30 ml/min (estimated by use of the Modification of Diet in Renal Disease (MDRD) formula) 8.Medical history of hypersensitivity to the study drugs or to drugs with similar chemical structures 9.History of severe or multiple allergies 10.Treatment with any other investigational drug within 3 months before trial entry 11.Progressive fatal disease 12.History of drug or alcohol abuse in the past 2 years 13.Condition after kidney transplantation 14.Serum potassium > 5.5 mmol/L 15.Pregnancy or breast feeding 16.Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomised partner. 17.Acute myocardial infarction, open heart surgery or cerebral event (stroke/TIA) within the previous 3 months 18.Any elective surgery during study participation 19.Uncontrolled unstable angina pectoris 20.Intake of Coumarin or coumarin derived compounds such as phenprocoumon (Marcumar) or warfarin (Coumadin, Warfant) 21.Intake of rifampicin or carbamazepine 22.HbA1c ≥ 6,5% 23.A Body Mass Index of > 35 kg/m² 24.CHF NYHA stage III – IV |
1.Diabetes mellitus Typ 1 2.Diabetes mellitus Typ 2 3.Unkontrollierter Bluthochdruck (systolisch >180 mmHg bzw. diastolisch >100 mmHg) 4.Akute Infektionen 5.Glomerulonephritis 6.Nierenerkrankung, die nicht durch Bluthochdruck verursacht wurde 7.GFR < 30 ml/min (MDRD-Formel) 8.Überempfindlichkeit gegen die Studienmedikation bzw. Medikamente mit chemisch ähnlichen Strukturen 9.Schwere oder multiple Allergien 10.Behandlung mit einer anderen Studienmedikation innerhalb der letzten 3 Monate 11.Progressive tödliche Krankheit 12.Drogen- oder Alkoholmissbrauch während der vergangenen 2 Jahre 13.Status post Nierentransplantation 14.Serum Kalium > 5.5 mmol/L 15.Schwangerschaft, Stillzeit 16.Sexuell aktive Frauen ohne sichere Verhütungsmethode (sichere Verhütungsmethoden sind z. B. Hormonimplantat, Pille, Intrauterinpessar, Abstinenz, sterilisierter Partner) 17.Akuter Myokardinfarkt, Operation am offenen Herzen, zerebrales Ereignis (Schlaganfall, TIA) innerhalb der letzten 3 Monate 18.Geplanter chirurgischer Eingriff in der Studienzeit 19.Unkontrollierte instable Angina pectoris 20.Einnahme von Cumarin bzw. chemisch ähnlicher Substanzen (Phenprocoumon, Warfarin) 21.Einnahme von Rifampicin or Carbamazepin 22.HbA1c ≥ 6,5% 23.BMI > 35 kg/m² 24.CHF NYHA Stadium III – IV |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Albumin/Creatinine Ratio (UACR) in 24h hour urine under standardized in house condition •24 hour urinary sodium excretion under standardized in house condition •Fasting cystatin C •Fasting serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) •Urinary N-acetyl-ß-o-glucosaminidase •Urinary nephrin •Urinary podocin •Fasting cGMP •Fasting serum ADMA •Fasting hsCRP •Fasting TGF-ß1 •Fasting serum and urinary IL-18 •Retinal endothelial function •Retinal microvascular blood flow •24h blood pressure measurements
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•Natriumausscheidung im 24h-Urin •Nüchtern Cystatin C •Nüchtern Serum und Urin-Werte des Parameters Neutrophil gelatinase-associated lipocalin (NGAL) •Urin-Werte des Parameters N-Acetyl-ß-o-Glukosaminidase •Urin-Werte des Parameters Nephrin •Urin-Werte des Parameters Podocin •Nüchtern cGMP •Nüchtern Serum ADMA •Nüchtern hsCRP •Nüchtern TGF ß1 •Nüchtern Serum und Urinwerte des Parameters IL-18 •Retinale Endothelfunktion •Retinaler mikrovaskulärer Blutfluss •24h Blutdruck
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after approx. 16 weeks of treatment |
nach ~ 16 Wochen Behandlung |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
exploratorisch, mechanistisch |
exploratory, mechanistic |
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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
| 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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After 6 study visits, approx. 16 weeks of treatment |
Nach 6 Studienvisiten, etwas 16 Wochen Behandlung |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |