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Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (TEMPO3:4)

30 maggio 2017 aggiornato da: Otsuka Pharmaceutical Development & Commercialization, Inc.

A Phase 3, Multi-center, Double-blind, Placebo-controlled, Parallel-arm Trial to Determine Long-term Safety and Efficacy of Oral Tolvaptan Tablets Regimens in Adult Subjects With Autosomal Dominant Polycystic Kidney Disease

This study's purpose is to evaluate the long-term safety and efficacy of tolvaptan versus placebo in patients with ADPKD.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

This study evaluated whether or not tolvaptan is potentially beneficial, while maintaining an adequate safety profile, by reducing the rate of total kidney volume increase, while impacting the onset, severity, and progression of other important consequences of ADPKD.

During the 3-week titration phase, tolvaptan or placebo was titrated in weekly intervals from lowest to highest tolerated levels given in split-dose regimens of 45/15 mg, 60/30 mg and 90/30 mg orally upon awakening and approximately 9 hours later. As soon as a subject could not tolerate a given dose, the titration phase was over and the maintenance phase began at the dose level tolerated. The maintenance phase lasted to Month 36. Subjects were able to titrate down at any point during the study. Subjects were able to titrate up during the maintenance phase with Medical Monitor approval.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

1445

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Argentina
      • Buenos Aires, Argentina, 1425
        • Instituto de Nefrología, Nefrology SA
      • Buenos Aires, Argentina, 1602
        • Hospital Municipal de Vicente Lopez, Dr Bernardo Houssay
      • Buenos Aires, Argentina, B1664INZ
        • Hosptial Universitario Austral
      • Cordoba, Argentina, X5000IUP
        • Sanatorio Allende
      • Cordoba, Argentina, X5016KEA
        • Hospital Privado-Centro Medico de Cordoba
  • Australia
      • Adelaide, Australia, 5000
        • Royal Adelaide Hospital
      • Adelaide, Australia, 5011
        • Queen Elizebeth Hospital
      • Brisbane, Australia, 4102
        • Princess Alexandra Hospital
      • Melbourne, Australia, 3050
        • Royal Melbourne Hospital
      • Melbourne, Australia, 3121
        • Melbourne Renal Research Group
      • Perth, Australia, 6054
        • Royal Perth Hospital
      • Sydney, Australia, 2065
        • Royal North Shore Hospital
      • Sydney, Australia, 2145
        • Westmead Hospital
  • Belgio
      • Brussel, Belgio, 1090
        • UZ Brussel
      • Brussels, Belgio, 1200
        • UCL-St Luc
      • Gent, Belgio, 9000
        • UZ Gent
  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H1v8
        • Queen Elizabeth II Health Science Center, Division of Nephrology
    • Quebec
      • Montreal, Quebec, Canada, H3A1A1
        • Royal Victoria Hospital
      • Montreal, Quebec, Canada, H4J1C5
        • Hospital du Sacre- Coeur de Montreal
  • Danimarca
      • Herlev, Danimarca, 2730
        • Herlev Amtssygehus
      • Odense, Danimarca, 5000
        • Odense Universitetshospital
  • Federazione Russa
      • Kemerovo, Federazione Russa, 650061
        • Kemerovo Medical Academy, Regional Clinical Hospital
      • Moscow, Federazione Russa, 123060
        • City Clinical Hospital #52
      • St. Petersburg, Federazione Russa, 191104
        • City Mariinskiy Hospital
      • St.-Petersburg, Federazione Russa, 194291
        • Leningrad Regional Clinical Hospital
      • Tomsk, Federazione Russa, 634063
        • Tomsk Regional Clinical Hospital
  • Francia
      • Bordeaux, Francia, 33076
        • CHU-Hopital Pellegrin
      • Caen Cedex, Francia, 14033
        • CHU - Hôpital Clémenceau
      • Lyon Cedex 3, Francia, 69437
        • Hôpital Edouard Herriot
      • Marseille, Francia, 13005
        • Hôpital de la Conception
      • Montpellier, Francia, 34295
        • CHU - Hôpital Lapeyronie
      • Paris, Francia, 75018
        • Hopital Bichat-Claude Bernard
      • Reims cedex, Francia, 51092
        • Centre Hospitalier Universitaire
      • Saint-Etienne Cedex 2, Francia, 42055
        • CHU - Hôpital Nord
      • Toulouse Cedex 09, Francia, 31059
        • Hopital Rangueil
  • Germania
      • Dresden, Germania, 1307
        • Universitätsklinikum Carl Gustav Carus
      • Düsseldorf, Germania, 40210
        • Nephrologische Gemeinschaftspraxis/Dialysezentrum
      • Essen, Germania, 45147
        • Klinik für Nieren- und Hochdruckkrankheiten
      • Freiburg, Germania, 78106
        • Universitätsklinikum Freiburg
      • Heidelberg, Germania, 69120
        • Universitätskliniken Heidelberg
      • Nuernberg, Germania, 90471
        • UH Erlangen/Nürnberg
  • Giappone
      • Chiba, Giappone, 2608677
        • Chiba University Hospital
      • Chiba, Giappone, 2608712
        • National Hospital Organization Chiba-East Hospital
      • Fukuoka, Giappone, 8128582
        • Kyusyu University Hospital
      • Fukushima, Giappone, 9601295
        • Fukushima Medical University Hospital
      • Hiroshima, Giappone, 7348551
        • Hiroshima University Hospital
      • Kumamoto, Giappone, 8608556
        • Kumamoto Univeristy Hospital
      • Kyoto, Giappone, 6068507
        • Kyoto University Hospital
      • Kyoto, Giappone, 612-8555
        • National Hospital Organization Kyoto Medical Center
      • Niigata, Giappone, 9518520
        • Niigata University Medical & Dental Hospital
      • Osaka, Giappone, 5500015
        • Ohno Memorial Hospital
      • Saitama, Giappone, 3308503
        • Saitama Medical Center Jichi Medical University
    • Aichi
      • Toyoake, Aichi, Giappone, 4701192
        • Fujita Health University Hospital
    • Hokkaido
      • Sapporo, Hokkaido, Giappone, 608648
        • Hokkaido University Hospital
    • Kanagawa
      • Isehara, Kanagawa, Giappone, 2591193
        • Tokai University Hospital
      • Kawasaki, Kanagawa, Giappone, 2138587
        • Toranomon Hospital Kajigaya
      • Sagamihara, Kanagawa, Giappone, 2288555
        • Kitasato University Hospital
    • Miyagi
      • Sendai, Miyagi, Giappone, 9808574
        • Tohoku University Hospital
    • Osaka
      • Osaka-City, Osaka, Giappone, 5458586
        • Osaka City University Hospital
      • Suita, Osaka, Giappone, 5650871
        • Osaka University Hospital
    • Saitama
      • Kasukabe, Saitama, Giappone, 3440035
        • Shuwa General Hospital
      • Kawagoe, Saitama, Giappone, 3508500
        • Saitama Medical Center
    • Shizuoka
      • Hamamatsu, Shizuoka, Giappone, 4313192
        • Hamamatsu University School of Medicine, University Hospital
    • Tochigi
      • Shimotsuke, Tochigi, Giappone, 3290498
        • Jichi Medical School Hospital
    • Tokyo
      • Bunkyo-ku, Tokyo, Giappone, 1138603
        • Nippon Medical School Hospital
      • Bunkyo-ku, Tokyo, Giappone, 1138519
        • Tokyo Medical & Dental University Hospital, Faculty of Medicine
      • Itabashi-ku, Tokyo, Giappone, 1738606
        • Teikyo University Hospital
      • Minato-Ku, Tokyo, Giappone, 1058471
        • The jikei University Hospital
      • Minato-ku, Tokyo, Giappone, 1058470
        • Toranomon Hospital
      • Mitaka, Tokyo, Giappone, 1818611
        • Kyorin University Hospital
      • Shinjuku-ku, Tokyo, Giappone, 1628666
        • Tokyo Women's Medical University Hospital
  • Italia
      • Bergamo, Italia, 24128
        • Ospedali Riuniti di Bergamo
      • Milano, Italia, 20132
        • Università Vita e Salute, Ospedale San Raffaele
      • Modena, Italia, 41100
        • Policlinico di Modena
      • Napoli, Italia, 80131
        • Policlinico
      • Pavia, Italia, 27100
        • IRCCS Fondazione Salvatore Maugeri
  • Olanda
      • Amsterdam, Olanda, 1081 HV
        • VU Medisch Centrum
      • Groningen, Olanda, 9713 GZ
        • UMCG Groningen
  • Polonia
      • Ciechanow, Polonia, 06-400
        • Oddział Nefrologiczny Stacja Dializ
      • Gdansk, Polonia, 80-952
        • Akademickie Centrum Kliniczne AMG
      • Gdansk, Polonia, 80-952
        • Samodzielny Publiczny Szpital Kliniczny nr 1, Akademickie Centrum Kliniczne AMG
      • Krakow, Polonia, 31-501
        • Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Szpital Uniwersytecki w Krakowie
      • Lodz, Polonia, 90-153
        • SOP ZOZ Uniwersytecki Szpital Kliniczny
      • Lublin, Polonia, 20-954
        • Samodzielny Publiczny Szpital kliniczny Nr 4 w Lublinie
      • Warsaw, Polonia, 04-749
        • Miedzyleski Szpital Specjalistyczny w Warszawie
      • Warsaw, Polonia, 02-507
        • Klinika Chorób Wewnętrznych i Nefrologii
      • Warszawa, Polonia, 03-401
        • Szpital Praski p.w. Przemienienia Panskiego, Samodzielny Publiczny Zaklad Opieki Zdrowotnej
      • Warszawa, Polonia, 03-401
        • Szpital Praski, Samodzielny Publiczny ZOZ
      • Wroclaw, Polonia, 50-417
        • Akademicki Szpital Kliniczny im J Mikulicza Radeckiego
  • Regno Unito
      • Belfast, Regno Unito, BT9 7AB
        • Belfast City Hospital
      • Birmingham, Regno Unito, B15 2TH
        • Oueen Elizabeth Hospital
      • Brighton, Regno Unito, BN2 5BE
        • Sussex Renal Unit Royal Sussex County Hospital
      • Coventry, Regno Unito, CV2 2DX
        • Uhcw Mhs Trust
      • Edinburgh, Regno Unito, EH16 4SA
        • Royal Infirmary
      • Inverness, Regno Unito, IV2 3UJ
        • Raigmore Hospital
      • London, Regno Unito, NW3 2PF
        • Royal Free and University College Medical School
      • London, Regno Unito, SE5-9RS
        • King's College Hospital
      • London, Regno Unito, SW170RE
        • St. George's Hospital
      • Sheffield, Regno Unito, S5 7AU
        • Royal Hallamshire Hospital
      • Swansea, Regno Unito, SA6 6NL
        • Morriston Hospital
  • Romania
      • Bucharest, Romania, 22328
        • Institutul Clinic Fundeni
      • Bucharest, Romania, 10731
        • Spitalul Clinic de Nefrologie Dr. Carol Davila
      • Iasi, Romania, 700503
        • Spitalul Clinic "C.I.Parhon"
  • Stati Uniti
    • Alabama
      • Mobile, Alabama, Stati Uniti, 36617
        • University Of South Alabama
      • Mobile, Alabama, Stati Uniti, 36608
        • Coastal Clinical Research
    • California
      • Riverside, California, Stati Uniti, 92503
        • Apex Research of Riverside
      • Stanford, California, Stati Uniti, 94305-5114
        • Stanford University Medical Center
    • Colorado
      • Denver, Colorado, Stati Uniti, 80262
        • University of Colorado Health Sciences Center
    • Connecticut
      • New Haven, Connecticut, Stati Uniti, 06510
        • Yale University School of Medicine
    • Florida
      • Jacksonville, Florida, Stati Uniti, 32216
        • Jacksonville Center for Clinical Research
      • Port Charlotte, Florida, Stati Uniti, 33952
        • Coastal Nephrology Associates Research Center, LLC
    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30308
        • Emory University School of Medicine
    • Illinois
      • Chicago, Illinois, Stati Uniti, 60611
        • Northwestern University
    • Kansas
      • Kansas City, Kansas, Stati Uniti, 66160
        • University of Kansas Medical Center
    • Louisiana
      • Baton Rouge, Louisiana, Stati Uniti, 70809
        • Renal Associates of Baton Rough, L.L.C.
    • Maryland
      • Baltimore, Maryland, Stati Uniti, 21205
        • John Hopkins School of Medicine
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, Stati Uniti, 02111
        • Tufts- New England Medical Center
    • Minnesota
      • Rochester, Minnesota, Stati Uniti, 55905
        • Mayo Medical Center
    • New York
      • Buffalo, New York, Stati Uniti, 14215
        • Erie County Medical Center
      • Hawthorne, New York, Stati Uniti, 10532
        • Nephrology Associates of Westchester
      • New York, New York, Stati Uniti, 10032
        • Columbia University Medical Center
      • New York, New York, Stati Uniti, 10021
        • The Rogosin Institute
    • North Carolina
      • Chapel Hill, North Carolina, Stati Uniti, 27599
        • University of North Carolina, UNC, Kidney Center
      • Greenville, North Carolina, Stati Uniti, 27834
        • East Carolina University
    • Ohio
      • Cincinnati, Ohio, Stati Uniti, 45220
        • Kidney and Hypertension Center
      • Cleveland, Ohio, Stati Uniti, 44106
        • University Hospitals of Cleveland/Case
    • Oregon
      • Portland, Oregon, Stati Uniti, 97210
        • Northwest Renal Clinic, Inc.
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stati Uniti, 19104
        • University of Pennsylvania Medical Center
    • South Carolina
      • Charleston, South Carolina, Stati Uniti, 29405
        • Charleston Nephrology Associates
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37205
        • Nephrology Associates, P.C.
      • Nashville, Tennessee, Stati Uniti, 37232-1371
        • Vanderbilt University Medical Center
    • Virginia
      • Charlottesville, Virginia, Stati Uniti, 22908
        • University of Virginia, Nephrology Clinical Research Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 50 anni (Adulto)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Legal adult age and able to give Informed Consent.
  • Adult subjects with a diagnosis of ADPKD. A diagnosis of ADPKD (age 18 or 20-50) required several cysts in each kidney (3 if by sonography, 5 if by CT or MRI) in those with a family history of ADPKD and 10 cysts (by any radiologic method) in each kidney and exclusion of other cystic kidney diseases if there was no family history.
  • Willingness to comply with reproductive precautions, if female.
  • Estimated creatinine clearance ≥ 60 mL/min. Estimated from serum creatinine during screening using Cockcroft-Gault with correction for gender and race, where possible.
  • Rapidly progressive kidney growth (total volume ≥ 750 cc) by magnetic resonance imaging (MRI) at randomization.

Exclusion Criteria:

  • Prior exposure to tolvaptan or other experimental PKD therapies.
  • Currently taking medication for purpose of affecting PKD cysts.
  • Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods.
  • In the opinion of the study investigator or sponsor may present a safety risk or confound study objectives.
  • Patients who are unlikely to adequately comply with study procedures.
  • Patients having contraindications to MRI.
  • Patients taking medications or having any illnesses likely to affect ADPKD outcomes.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Tolvaptan
Participants received the highest tolerated split-dose regimen (upon awakening and 9 hours later) of tolvaptan 45/15 mg, 60/30 mg, or 90/30 mg orally for 36 months.
Droga: Tolvaptan
Tolvaptan was supplied as tablets.
Altri nomi:
  • OPC-41061
  • OPC-156
Comparatore placebo: Placebo
Participants received placebo (upon awakening and 9 hours later) orally for 36 months.
Droga: Placebo
Placebo was supplied as tablets.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage Change Per Year in Total Kidney Volume From Baseline to Month 36
Lasso di tempo: Baseline to Month 36
Kidney volume was assessed in T1-weighted magnetic resonance images collected at each study site and sent to a central reviewing facility. At the central reviewing facility, blinded radiologists used proprietary software to measure the volume of both kidneys.
Baseline to Month 36

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of ADPKD Clinical Progression Events Per 100 Follow-up Years From Baseline to Month 36
Lasso di tempo: Baseline to Month 36
These ADPKD events in the key secondary Outcome Measure were selected on the basis of their potential relationship to progressing cystogenesis. Reducing the rate of cyst development and expansion would likely slow the progression of ADPKD. The 4 events were: (1) Onset or progression of hypertension (someone is hypertensive if they have > 139 mmHg systolic blood pressure [BP], > 89 mmHg diastolic BP, or if they are taking antihypertensive medication at any BP level); (2) severe renal pain requiring medical intervention; (3) worsening albuminuria (by category, see below); and (4) worsening renal function, defined as a 25% decrease in 1/serum creatinine from Baseline. Albuminuria was assessed using spot urine albumin/creatinine ratio measurements (all measurements in mg/mmol). Categories included normal (< 2.8 female or < 2.0 male), microalbuminuria (2.8-28 female or 2.0-20 male), and overt proteinuria (> 28 female or > 20 male.
Baseline to Month 36
Change in Renal Function Per Year From Week 3 to Month 36
Lasso di tempo: Week 3 to Month 36
Renal function was assessed using serum creatinine measurements and was estimated using 1/serum creatinine. The formula for 1/serum creatinine is: 1/Pcr, where Pcr = serum creatinine concentration (mg/dL). The change in renal function per year was based on the slope of change, obtained by regressing renal function data against time by subject.
Week 3 to Month 36
Change in Mean Arterial Blood Pressure Per Year in Non-hypertensive Participants From Baseline to Month 36
Lasso di tempo: Baseline to Month 36
For participants who were non-hypertensive (systolic BP ≤ 139 mmHg and diastolic BP ≤ 89 mmHg without taking antihypertensive medications) at baseline, mean arterial blood pressure was measured at scheduled clinic visits up to the point of exposure to antihypertensive therapy for any reason. The change in mean arterial blood pressure per year was based on the slope of blood pressure, obtained by regressing blood pressure against time by subject.
Baseline to Month 36
Area Under the Concentration-time Curve of Change in Renal Pain From Baseline to Month 36
Lasso di tempo: At screening, Baseline, Day 1, every 4 months up to month 36/early tremination (ET), follow-up visit 1 and 2
Change from baseline in renal pain was assessed by a 0 to 10 pain scale as average area under the concentration-time curve (AUC) between baseline and the last trial visit or the last visit prior to initiating medical (eg, narcotic or anti-nociceptives [eg, tricyclic antidepressants]) or surgical therapy for pain. In the pain scale, score 0 represented no pain at all and score 10 represented the worst pain. A negative change score indicates less pain. AUC of renal pain was derived from renal pain scores within treatment period and was calculated using the trapezoidal rule, by dividing the number of days between the first and last assessment.
At screening, Baseline, Day 1, every 4 months up to month 36/early tremination (ET), follow-up visit 1 and 2
Number of Hypertensive Events Per 100 Follow-up Years in Non-hypertensive Participants From Baseline to Month 36
Lasso di tempo: Baseline to Month 36
A hypertensive event was defined as a change from non-hypertensive (systolic BP ≤ 139 mmHg and diastolic BP ≤ 89 mmHg without taking antihypertensive medications) status to 1 of 3 conditions: (1) High pre-hypertensive (systolic BP [sBP] > 129 mmHg and/or diastolic BP [dBP] > 84 mmHg), (2) hypertensive (sBP > 139 mmHg and/or dBP > 89 mmHg), or (3) requiring antihypertensive therapy.
Baseline to Month 36
Percentage of Participants With a Clinically Sustained Decrease of Blood Pressure Leading to a Sustained Reduction in Antihypertensive Therapy From Baseline to Month 36
Lasso di tempo: Baseline to Month 36
Baseline to Month 36

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaboratori

Otsuka Pharmaceutical Co., Ltd.

Investigatori

  • Investigatore principale: Vicente Torres, MD, PhD, Mayo Medical Center
  • Direttore dello studio: Frank Czerwiec, MD, PhD, Otsuka Pharmaceutical Development and Commercialization, Inc.
  • Direttore dello studio: Osamu Sato, Otsuka Pharmaceutical Corporation, Ltd. Japan

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 gennaio 2007

Completamento primario (Effettivo)

1 gennaio 2012

Completamento dello studio (Effettivo)

1 gennaio 2012

Date di iscrizione allo studio

Primo inviato

26 gennaio 2007

Primo inviato che soddisfa i criteri di controllo qualità

29 gennaio 2007

Primo Inserito (Stima)

30 gennaio 2007

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

2 luglio 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

30 maggio 2017

Ultimo verificato

1 maggio 2017

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 156-04-251
  • 2006-002768-24 (Numero EudraCT)

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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