E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult dominant polycystic kidney disease (ADPKD) |
Polycystsisk nyresygdom |
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E.1.1.1 | Medical condition in easily understood language |
Adult dominant polycystic kidney disease (ADPKD) |
Polycystsisk nyresygdom |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physical Phenomena [G01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036046 |
E.1.2 | Term | Polycystic kidney, autosomal dominant |
E.1.2 | System Organ Class | 100000004850 |
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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 purpose of this trial is to ivestige if tolvatans improve renal blood flow in ADPKD |
Formålet er at måle akutte effekter af tolvaptatan på den renale hæmodynamik hos patienter med ADPKD. |
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E.2.2 | Secondary objectives of the trial |
The purpose of this trial is to ivestige if tolvatans improve renal blood flow in ADPKD |
Formålet er at måle akutte effekter af tolvaptatan på den renale hæmodynamik (RPF, GFR, FF og RVR), blodtrykket (cBP, bBP) samt flere vasoaktive hormoner (PRC, p-Ang-II, p-Aldo, p.AVP) hos patienter med ADPKD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age > 18 years
Diagnosis with ADPKD
Informed consent
Contraception for fertile women |
• Alder >18 år
• Patienter med diagnosen ADKPD (Ravine–kriterier), diagnosticeret ved genetisk testning for PKD1 (>85%) og PKD2 mutationer, eller UL-defineret (9-10):
1. Patienter uden familiær ADKPD anamnese, skal have mere end 10 cyster i hver nyre, andre årsager til ekstra- eller renale cyster skal være udelukket.
2. Patienter med familiær ADKPD anamnese:
18-39 år og have mindst 3 cyster uni- eller bilateralt
40-59 år og have mindst 2 cyster eller flere cyster i hver nyre
>60 år og have mindst 4 cyster i hver nyre
• Nyrefunktion svarende til kronisk nyresygdom stadium 1-3 (eGFR> 30 mL/min/1,73 m2)
• Underskrevet samtykke
• Fertile kvinder skal anvende sikker antikonception i hele forsøgsperioden, og i en periode efterfølgende, der svarer til 5 gange plasma halveringstiden, dvs mindst 2 døgn. (sikker antikonception defineres som: p-piller, spiral, depotinjektion af gestagen, subdermal implantation, hormonal vaginalring samt transdermal depotplaster)
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E.4 | Principal exclusion criteria |
• Renal transplantation
• Operation in the kidnety
• Diabetes mellitus
• Neoplastic conditions
• Pregnancy, nursing
• Unwillingness to participate
• eGFR > 30
• Intolerans towrds tolvaptan
• Alkohol or medical abuse,
• BP >>170/110 blodtryk despite regulation
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• Tidligere nyretransplantation
• Operation på nyrerne
• Diabetes mellitus
• Aktuelle neoplastiske lidelser
• Graviditet, mindre end 6 måneder efter fødsel eller amning
• Manglende ønske om at deltage
• eGFR > 30
• Intolerans overfor eller uacceptable bivirkninger af tolvaptan
• Alkoholmisbrug, dvs. >14 genstande/uge for kvinder og > 21 genstande/uge for mænd
• Medicin- eller stofmisbrug
• Uacceptabelt højt dvs. >170/110 blodtryk på trods af regulering antihypertesiv medicin
• Uacceptable bivirkninger den antihypertensive medicin, der gives som baggrundsmedicin i projektperioden.
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E.5 End points |
E.5.1 | Primary end point(s) |
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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) |
GFR, RVR, FF
Brachial and central BP
PRC, p-Ang-II, p-Aldo, p-AVP
Urinflow, u-Na, u-K, u-albumin, u-creatinin, u-osmolalitet, u-AQP-2 in 24 hour urine
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GFR, RVR, FF
Brakialt og centralt blodtryk
PRC, p-Ang-II, p-Aldo, p-AVP
Urinflow, u-Na, u-K, u-albumin, u-creatinin, u-osmolalitet, u-AQP-2 i døgnurin
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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 | 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
| 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 | 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 sunsbject |
Sidste forsøgspersones sidste besøg |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |