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

2017年5月30日 更新者：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.

研究概览

地位

完全的

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (实际的)

1445

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

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

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 50年 (成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：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.
药品：Tolvaptan
Tolvaptan was supplied as tablets.
其他名称：
  • OPC-41061
  • OPC-156
安慰剂比较：Placebo
Participants received placebo (upon awakening and 9 hours later) orally for 36 months.
药品：Placebo
Placebo was supplied as tablets.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Percentage Change Per Year in Total Kidney Volume From Baseline to Month 36
大体时间：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

次要结果测量

结果测量
措施说明
大体时间
Number of ADPKD Clinical Progression Events Per 100 Follow-up Years From Baseline to Month 36
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：Baseline to Month 36
Baseline to Month 36

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Otsuka Pharmaceutical Development & Commercialization, Inc.

合作者

Otsuka Pharmaceutical Co., Ltd.

调查人员

  • 首席研究员：Vicente Torres, MD, PhD、Mayo Medical Center
  • 研究主任：Frank Czerwiec, MD, PhD、Otsuka Pharmaceutical Development and Commercialization, Inc.
  • 研究主任：Osamu Sato、Otsuka Pharmaceutical Corporation, Ltd. Japan

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2007年1月1日

初级完成 (实际的)

2012年1月1日

研究完成 (实际的)

2012年1月1日

研究注册日期

首次提交

2007年1月26日

首先提交符合 QC 标准的

2007年1月29日

首次发布 (估计)

2007年1月30日

研究记录更新

最后更新发布 (实际的)

2017年7月2日

上次提交的符合 QC 标准的更新

2017年5月30日

最后验证

2017年5月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

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

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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