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

30. mai 2017 oppdatert 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

1445

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • 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
  • Belgia
      • Brussel, Belgia, 1090
        • UZ Brussel
      • Brussels, Belgia, 1200
        • UCL-St Luc
      • Gent, Belgia, 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
  • Danmark
      • Herlev, Danmark, 2730
        • Herlev Amtssygehus
      • Odense, Danmark, 5000
        • Odense Universitetshospital
  • Den russiske føderasjonen
      • Kemerovo, Den russiske føderasjonen, 650061
        • Kemerovo Medical Academy, Regional Clinical Hospital
      • Moscow, Den russiske føderasjonen, 123060
        • City Clinical Hospital #52
      • St. Petersburg, Den russiske føderasjonen, 191104
        • City Mariinskiy Hospital
      • St.-Petersburg, Den russiske føderasjonen, 194291
        • Leningrad Regional Clinical Hospital
      • Tomsk, Den russiske føderasjonen, 634063
        • Tomsk Regional Clinical Hospital
  • Forente stater
    • Alabama
      • Mobile, Alabama, Forente stater, 36617
        • University of South Alabama
      • Mobile, Alabama, Forente stater, 36608
        • Coastal Clinical Research
    • California
      • Riverside, California, Forente stater, 92503
        • Apex Research of Riverside
      • Stanford, California, Forente stater, 94305-5114
        • Stanford University Medical Center
    • Colorado
      • Denver, Colorado, Forente stater, 80262
        • University of Colorado Health Sciences Center
    • Connecticut
      • New Haven, Connecticut, Forente stater, 06510
        • Yale University School Of Medicine
    • Florida
      • Jacksonville, Florida, Forente stater, 32216
        • Jacksonville Center for Clinical Research
      • Port Charlotte, Florida, Forente stater, 33952
        • Coastal Nephrology Associates Research Center, LLC
    • Georgia
      • Atlanta, Georgia, Forente stater, 30308
        • Emory University School of Medicine
    • Illinois
      • Chicago, Illinois, Forente stater, 60611
        • Northwestern University
    • Kansas
      • Kansas City, Kansas, Forente stater, 66160
        • University of Kansas Medical Center
    • Louisiana
      • Baton Rouge, Louisiana, Forente stater, 70809
        • Renal Associates of Baton Rough, L.L.C.
    • Maryland
      • Baltimore, Maryland, Forente stater, 21205
        • John Hopkins School of Medicine
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, Forente stater, 02111
        • Tufts- New England Medical Center
    • Minnesota
      • Rochester, Minnesota, Forente stater, 55905
        • Mayo Medical Center
    • New York
      • Buffalo, New York, Forente stater, 14215
        • Erie County Medical Center
      • Hawthorne, New York, Forente stater, 10532
        • Nephrology Associates of Westchester
      • New York, New York, Forente stater, 10032
        • Columbia University Medical Center
      • New York, New York, Forente stater, 10021
        • The Rogosin Institute
    • North Carolina
      • Chapel Hill, North Carolina, Forente stater, 27599
        • University of North Carolina, UNC, Kidney Center
      • Greenville, North Carolina, Forente stater, 27834
        • East Carolina University
    • Ohio
      • Cincinnati, Ohio, Forente stater, 45220
        • Kidney and Hypertension Center
      • Cleveland, Ohio, Forente stater, 44106
        • University Hospitals of Cleveland/Case
    • Oregon
      • Portland, Oregon, Forente stater, 97210
        • Northwest Renal Clinic, Inc.
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater, 19104
        • University of Pennsylvania Medical Center
    • South Carolina
      • Charleston, South Carolina, Forente stater, 29405
        • Charleston Nephrology Associates
    • Tennessee
      • Nashville, Tennessee, Forente stater, 37205
        • Nephrology Associates, P.C.
      • Nashville, Tennessee, Forente stater, 37232-1371
        • Vanderbilt University Medical Center
    • Virginia
      • Charlottesville, Virginia, Forente stater, 22908
        • University of Virginia, Nephrology Clinical Research Center
  • Frankrike
      • Bordeaux, Frankrike, 33076
        • CHU-Hopital Pellegrin
      • Caen Cedex, Frankrike, 14033
        • CHU - Hôpital Clémenceau
      • Lyon Cedex 3, Frankrike, 69437
        • Hôpital Edouard Herriot
      • Marseille, Frankrike, 13005
        • Hopital de la Conception
      • Montpellier, Frankrike, 34295
        • CHU - Hôpital Lapeyronie
      • Paris, Frankrike, 75018
        • Hôpital Bichat-Claude Bernard
      • Reims cedex, Frankrike, 51092
        • Centre Hospitalier Universitaire
      • Saint-Etienne Cedex 2, Frankrike, 42055
        • Chu - Hopital Nord
      • Toulouse Cedex 09, Frankrike, 31059
        • Hopital Rangueil
  • 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
  • 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
  • Nederland
      • Amsterdam, Nederland, 1081 HV
        • VU Medisch Centrum
      • Groningen, Nederland, 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
        • Międzyleski 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
  • 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"
  • Storbritannia
      • Belfast, Storbritannia, BT9 7AB
        • Belfast City Hospital
      • Birmingham, Storbritannia, B15 2TH
        • Oueen Elizabeth Hospital
      • Brighton, Storbritannia, BN2 5BE
        • Sussex Renal Unit Royal Sussex County Hospital
      • Coventry, Storbritannia, CV2 2DX
        • Uhcw Mhs Trust
      • Edinburgh, Storbritannia, EH16 4SA
        • Royal Infirmary
      • Inverness, Storbritannia, IV2 3UJ
        • Raigmore Hospital
      • London, Storbritannia, NW3 2PF
        • Royal Free and University College Medical School
      • London, Storbritannia, SE5-9RS
        • King's College Hospital
      • London, Storbritannia, SW170RE
        • St. George's Hospital
      • Sheffield, Storbritannia, S5 7AU
        • Royal Hallamshire Hospital
      • Swansea, Storbritannia, SA6 6NL
        • Morriston Hospital
  • Tyskland
      • Dresden, Tyskland, 1307
        • Universitatsklinikum Carl Gustav Carus
      • Düsseldorf, Tyskland, 40210
        • Nephrologische Gemeinschaftspraxis/Dialysezentrum
      • Essen, Tyskland, 45147
        • Klinik für Nieren- und Hochdruckkrankheiten
      • Freiburg, Tyskland, 78106
        • Universitatsklinikum Freiburg
      • Heidelberg, Tyskland, 69120
        • Universitätskliniken Heidelberg
      • Nuernberg, Tyskland, 90471
        • UH Erlangen/Nürnberg

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 50 år (Voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Legemiddel: Tolvaptan
Tolvaptan was supplied as tablets.
Andre navn:
  • OPC-41061
  • OPC-156
Placebo komparator: Placebo
Participants received placebo (upon awakening and 9 hours later) orally for 36 months.
Legemiddel: Placebo
Placebo was supplied as tablets.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage Change Per Year in Total Kidney Volume From Baseline to Month 36
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of ADPKD Clinical Progression Events Per 100 Follow-up Years From Baseline to Month 36
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Baseline to Month 36
Baseline to Month 36

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Samarbeidspartnere

Otsuka Pharmaceutical Co., Ltd.

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. januar 2007

Primær fullføring (Faktiske)

1. januar 2012

Studiet fullført (Faktiske)

1. januar 2012

Datoer for studieregistrering

Først innsendt

26. januar 2007

Først innsendt som oppfylte QC-kriteriene

29. januar 2007

Først lagt ut (Anslag)

30. januar 2007

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

2. juli 2017

Siste oppdatering sendt inn som oppfylte QC-kriteriene

30. mai 2017

Sist bekreftet

1. mai 2017

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere