E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SIADH (Syndrome of inappropriate ADH production) Overhydration Hyponatrimia |
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E.1.1.1 | Medical condition in easily understood language |
Overhydration Decreased salt |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021038 |
E.1.2 | Term | Hyponatremia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040626 |
E.1.2 | Term | SIADH |
E.1.2 | System Organ Class | 10014698 - Endocrine 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 |
To Investigate the effects of tolvaptan on the nitric oxide system |
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E.2.2 | Secondary objectives of the trial |
The purpose is to investigate the effects of tolvaptan on renal sodium and water handling(GFR, UV, CH20, u-AQP2, u-ENaCαβγ, u-NCC, u-NK2CC, CNa, FENa, CK, FEK), plasma concentrations of vasoactive hormoner (renin, angiotensin II, aldosterone, atrial natriuretic peptide, brain natriuretic peptide and endotehline), central blood pressure, pulse wave velocity (PWV) og augmentation index, at baseline and during inhibition of nitric oxide synthesis with L-NMMA in healthy subjects |
Formålet er at måle effekten af tolvaptan på NO’s effekt på nyrernes behandling af vand og natrium (GFR, UV, CH20, u-AQP2, u-ENaCαβγ, u-NCC, u-NK2CC, CNa, FENa, CK, FEK), vasoaktive hormoner (PRC, p-AngII, p-Aldo, p-AVP, p-ANP, p-BNP og p-Endot), centralt blodtryk, pulse wave velocity (PWV) og augmentation index, basalt og under hæmning af nitrogenoxid syntesen hos raske forsøgspersoner. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Men and women (fertile women must use contraceptives) Age 18-40 years BMI between 18.5-30 kg/m2 Informed consent |
Mænd og kvinder Alder 18-40 år BMI mellem 18,5-30 kg/m2 Underskrevet samtykke
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E.4 | Principal exclusion criteria |
a) Arterial hypertension (ofiice BP over 140 mmHg systolisc and/or 90 mmHg diastolic) b) Clincal signs of heart, lung, liver, kidney, brain, endocrine or neplastic diseases c) Alcoholabuse d) Drugabuse. e) Medical treatment, except anticontraceptives f) Smoking g) Pregnancy or nursing h) Clinical important abnormalities in blood or urine samples or during he alt examination i) Clinical important abnormalities in ECG j) Bloddonation within a month of first treatment period k) Allergies towards Tolvaptan. l) Fertile women must use contraceptives |
a) Arteriel hypertension dvs. konsultationsblodtryk over 140 mmHg systolisk og/eller 90 mmHg diastolisk b) Betydende kliniske tegn på hjertesygdom, sygdomme i lunger, lever, nyrer, endokrine organer eller hjernen samt neoplastiske lidelser c) Alkoholmisbrug, dvs. >14 genstande/uge for kvinder og > 21 genstande/uge for mænd d) Stofmisbrug. e) Medicinsk behandling fraset orale antikonceptiva. f) Aktiv rygning. g) Graviditet eller amning. h) Klinisk betydende abnorme fund ved blod- eller urinprøven ved inklusionsundersøgelsen i) Klinisk betydende kliniske forandringer i elektrokardiogram j) Bloddonation indenfor den seneste måned inden undersøgelsesdagen i første forsøgssekvens. k) Allergi overfor Tolvaptan. l) Fertile kvinder skal anvende sikker antikonception i hele forsøgsperioden, og i en periode efterfølgende, der svarer til 5 gange plasma halveringstiden (sikker antikonception defineres som: p-piller, spiral, depotinjektion af gestagen, subdermal implantation, hormonal vaginalring samt transdermal depotplaster). Ellers ekskluderes disse.
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E.5 End points |
E.5.1 | Primary end point(s) |
CH2O (Free water clereance) |
Fridt vands clereance |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Kidney function: GFR, UV, CH20, protein excretion from tubular sodium and water channels (u-AQP-2, u-ENaCβ, u-ENaCγ, u-NCC, u-NK2CC), Sodium excretion (CNa, FENa), potassium excretion (CK, FEK) Central blood pressure, pulse wave velocity and augmentation index, Vasoactive hormones: p-Renin, p-Angiotensin II, p-Aldosterone, p-AVP , p-ANP (atrial natriuretic peptide), p-BNP (brain natriuretic peptide) og p-Endotheline-1 |
Nyrefunktion: GFR, UV, CH20, u-AQP-2, u-ENaCβ, u-ENaCγ, u-NCC, u-NK2CC, CNa, FENa, CK, FEK Det centrale blodtryk, pulsbølgehastighed og augmentation index, Vasoaktive hormoner: PRC, p-AngII, p-Aldo, p-AVP, p-ANP, p-BNP og p-Endot
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.8.1.1 | Randomised | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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The last visit of the last subject |
Det sidste besøg af den sidst forsøgsperson |
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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 |