| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Autosomal Dominant Policiytic Kidney Disease |
| Malattia del rene policistico autosomico dominante |
|
| E.1.1.1 | Medical condition in easily understood language |
| Autosomal Dominant Policystic Kidney Disease |
| Malattia del rene policistico autosomico dominante |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
| 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 |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the effect of 4-week Tolvaptan and Octreotide LAR combination therapy as compared to Tolvaptan and Placebo combination therapy on GFR, as assessed by the Iohexol Plasma Clearance Technique, in 20 ADPKD patients with normal kidney function (GFR: >80 and <120 ml/min/1.73m2) or hyperfiltration (GFR >120 ml/min/1.73m2). |
| Valutare l’effetto sul GFR (misurato con la tecnica della clearance dello ioexolo) della somministrazione per quattro settimane di Tolvaptan e Octreotide LAR rispetto a Tolvaptan e placebo, in 20 pazienti affetti da ADPKD con funzione renale normale (GFR: >80 e <120 ml/min/1.73m2) o iperfiltranti (GFR >120 ml/min/1.73m2). |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the effect of 4-week Tolvaptan and Octreotide LAR combination therapy as compared to Tolvaptan and Placebo Combination therapy on TKV percentage changes as assessed by MRI, in 20 ADPKD patients with normal kidney function or hyperfiltration. |
| Valutare l’effetto sulle variazioni percentuali del TKV (misurato con la risonanza magnetica) della somministrazione per quattro settimane di Tolvaptan e Octreotide LAR rispetto a Tolvaptan e placebo, in 20 pazienti affetti da ADPKD con funzione renale normale o iperfiltranti. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adult (>18-yr-old) men and women, with a clinical and ultrasonographic diagnosis of ADPKD;
2. Serum creatinine < 1.0 mg/dl (for man) and < 1.2 mg/dl (for woman) and changes in serum creatinine (and creatinine clearance when available) <30% over the last six months;
3. Creatinine clearance > 80 ml/min/1.73m2 measured one to two weeks apart during the pre-screening period;
4. GFR ≥ 80 ml/min/1.73m2 (by iohexol plasma clearance technique) at screening and baseline evaluations;
5. TKV ranging between 1000 and 2000 ml at screening (by ultrasound imaging) and at baseline (by MRI) evaluations;
6. Female participants must be of non-childbearing potential or must agree to abstinence or use a highly effective form of contraception;
7. Written informed consent.
|
1. Donne e uomini di età >18 anni, con diagnosi clinica ed ecografica di ADPKD;
2. Creatinina sierica < 1.0 mg/dl (per gli uomini) e < 1.2 mg/dl (per le donne) e variazioni nei valori di creatinina sierica (e clearance della creatinina quando disponibile) <30% nei 6 mesi precedenti l’inizio dello studio;
3. Clearance della creatinina > 80 ml/min/1.73m2 misurata con un intervallo da una a due settimane durante il periodo pre-screening;
4. GFR ≥ 80 ml/min/1.73m2 (misurato con la clearance plasmatica dello ioexolo) allo screening e al basale;
5. TKV compreso tra 1000 e 2000 ml allo screening (determinato con l’ecografia) e al basale (determinato con la risonanza magnetica);
6. Le donne che parteciperanno allo studio devono essere non fertili o devono accettare di praticare l’astinenza o utilizzare un metodo contraccettivo efficace per tutta la durata dello studio;
7. Consenso informato scritto.
|
|
| E.4 | Principal exclusion criteria |
1. Patients with concomitant systemic, renal parenchymal or urinary tract disease;
2. Diabetes;
3. Overt proteinuria (urinary protein excretion rate >1 g/24 hours);
4. Abnormal urinalysis suggestive of concomitant, clinically significant glomerular disease, urinary tract lithiasis, infection or obstruction, biliary tract lithiasis or obstruction;
5. Hemorrhagic or complicated cysts which might acutely affect kidney function and volumes;
6. QT-related ECG abnormalities;
7. Cancer and major systemic diseases that could prevent completion of the planned follow-up or interfere with data collection or interpretation;
8. Hypersensitivity to the IMP active substance or to any of the excipients or to benzazepine or benzazepine derivatives;
9. Concomitant treatment with drugs that may affect glomerular hemodynamics during the three months before the beginning of the study (including ACE inhibitors, angiotensin receptor blockers, aldosterone antagonists and non-steroideal anti-inflammatory medications);
10. Elevated liver enzymes and/or signs or symptoms of liver injury prior to initiation of treatment that meet the requirements for permanent discontinuation of tolvaptan
11. Patients with anuria, volume depletion and hypernatraemia
12. Patients who cannot perceive or respond to thirst
13. Ferro-magnetic prosthesis, aneurysm clips, severe claustrophobia or any other contraindication to MRI evaluation;
14. Psychiatric disorders and any condition that could prevent full comprehension of the purposes and risks of the study;
15. Pregnant or lactating;
16. Participation in another interventional clinical trial within the 4 weeks prior to screening.
|
1. Pazienti con malattie concomitanti sistemiche, parenchimali renali o a carico del tratto urinario;
2. Diabete;
3. Proteinuria conclamata (escrezione urinaria di proteine >1 g/24 ore);
4. Anomalie nell’analisi delle urine tali da far ipotizzare la presenza di malattie glomerulari concomitanti, litiasi, infezioni o ostruzione a carico delle vie urinarie, litiasi o ostruzione del tratto biliare;
5. Cisti emorragiche o complicate che potrebbero compromettere la funzione e il volume del rene;
6. Anomalie dell’ECG relative all’intervallo QT;
7. Cancro, malattie sistemiche importanti che potrebbero impedire il completamento del follow-up previsto dal protocollo o interferire con la raccolta o l’interpretazione dei dati;
8. Ipersensibilità al principio attivo del prodotto sperimentale o ad uno qualsiasi degli eccipienti o a benzazepine o loro derivati;
9. Trattamenti concomitanti con farmaci che potrebbero alterare l’emodinamica renale nei tre mesi precedenti l’inizio dello studio (inclusi ACE inibitori, antagonisti del recettore dell’angiotensina, antagonisti dell’aldosterone e farmaci antinfiammatori non steroidei);
10. Enzimi epatici elevati e/o segni o sintomi di danno epatico prima dell’inizio del trattamento, che soddisfino i requisiti per l’interruzione permanente di tolvaptan;
11. Pazienti con anuria, ipovolemia e ipernatremia;
12. Pazienti non in grado di avvertire o di rispondere allo stimolo della sete;
13. Protesi ferro-magnetiche, clip per aneurisma, claustrophobia grave o qualsiasi altra controindicazione alla risonanza magnetica;
14. Disordini psichiatrici e qualsiasi condizione che possa impedire la piena comprensione degli scopi e dei rischi dello studio;
15. Donne in gravidanza o allattamento;
16. Partecipazione ad un altro studio clinico interventistico nelle 4 settimane che precedono il periodo di screening.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Effect of 4-week Tolvaptan and Octreotide LAR combination therapy as compared to Tolvaptan and Placebo combination therapy on GFR, assessed
by the Iohexol Plasma Clearance Technique. |
| Valutare l’effetto sul GFR (misurato con la tecnica della clearance dello ioexolo) della somministrazione per quattro settimane di Tolvaptan e Octreotide LAR rispetto a Tolvaptan e placebo, in 20 pazienti affetti da ADPKD con funzione renale normale (GFR: >80 e <120 ml/min/1.73m2) o iperfiltranti (GFR >120 ml/min/1.73m2). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 4 weeks before the randomization, at baseline, 1,4,8,9,12 and 16 weeks after randomization |
| 4 settimane prima della randomizzazione, al basale, 1, 4, 8, 9, 12 e 16 settimane dopo la randomizzazione. |
|
| E.5.2 | Secondary end point(s) |
| Effect of 4-week Tolvaptan and Octreotide LAR combination therapy as compared to Tolvaptan and Placebo Combination therapy on TKV percentage changes assessed by MRI. |
| Valutare l’effetto sulle variazioni percentuali del TKV (misurato con la risonanza magnetica) della somministrazione per quattro settimane di Tolvaptan e Octreotide LAR rispetto a Tolvaptan e placebo, in 20 pazienti affetti da ADPKD con funzione renale normale o iperfiltranti. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| At baseline (randomization), 4, 8, 12 and 16 weeks after the randomization. |
| Al basale (randomizzazione), 4, 8,12 e 16 settimane dopo la randomizzazione. |
|
| 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 | Yes |
| 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 1 |
| 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 | Information not present in EudraCT |
| 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
|
| The natural conclusion of the clinical trial coincides with the closure of the study database. |
| Lo studio si definirà concluso al momento della chiusura del database. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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