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

30 mai 2017 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

1445

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 50 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: Tolvaptan
Tolvaptan was supplied as tablets.
Autres noms:
  • OPC-41061
  • OPC-156
Comparateur placebo: Placebo
Participants received placebo (upon awakening and 9 hours later) orally for 36 months.
Médicament: Placebo
Placebo was supplied as tablets.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage Change Per Year in Total Kidney Volume From Baseline to Month 36
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of ADPKD Clinical Progression Events Per 100 Follow-up Years From Baseline to Month 36
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: Baseline to Month 36
Baseline to Month 36

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborateurs

Otsuka Pharmaceutical Co., Ltd.

Les enquêteurs

  • Chercheur principal: Vicente Torres, MD, PhD, Mayo Medical Center
  • Directeur d'études: Frank Czerwiec, MD, PhD, Otsuka Pharmaceutical Development and Commercialization, Inc.
  • Directeur d'études: Osamu Sato, Otsuka Pharmaceutical Corporation, Ltd. Japan

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 janvier 2007

Achèvement primaire (Réel)

1 janvier 2012

Achèvement de l'étude (Réel)

1 janvier 2012

Dates d'inscription aux études

Première soumission

26 janvier 2007

Première soumission répondant aux critères de contrôle qualité

29 janvier 2007

Première publication (Estimation)

30 janvier 2007

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

2 juillet 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

30 mai 2017

Dernière vérification

1 mai 2017

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

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

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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