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

30 maj 2017 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

1445

Fas

  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 50 år (Vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Läkemedel: Tolvaptan
Tolvaptan was supplied as tablets.
Andra namn:
  • OPC-41061
  • OPC-156
Placebo-jämförare: Placebo
Participants received placebo (upon awakening and 9 hours later) orally for 36 months.
Läkemedel: Placebo
Placebo was supplied as tablets.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Percentage Change Per Year in Total Kidney Volume From Baseline to Month 36
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of ADPKD Clinical Progression Events Per 100 Follow-up Years From Baseline to Month 36
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: Baseline to Month 36
Baseline to Month 36

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Samarbetspartners

Otsuka Pharmaceutical Co., Ltd.

Utredare

  • Huvudutredare: Vicente Torres, MD, PhD, Mayo Medical Center
  • Studierektor: Frank Czerwiec, MD, PhD, Otsuka Pharmaceutical Development and Commercialization, Inc.
  • Studierektor: Osamu Sato, Otsuka Pharmaceutical Corporation, Ltd. Japan

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 januari 2007

Primärt slutförande (Faktisk)

1 januari 2012

Avslutad studie (Faktisk)

1 januari 2012

Studieregistreringsdatum

Först inskickad

26 januari 2007

Först inskickad som uppfyllde QC-kriterierna

29 januari 2007

Första postat (Uppskatta)

30 januari 2007

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

2 juli 2017

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

30 maj 2017

Senast verifierad

1 maj 2017

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

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

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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