8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (NOCTURNE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01451827
Recruitment Status : Completed
First Posted : October 14, 2011
Last Update Posted : June 19, 2014
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary:
The purpose of this study is to compare the short-term effects of two tolvaptan formulations in patients with ADPKD.

Condition or disease Intervention/treatment Phase
Autosomal Dominant Polycystic Kidney Disease Drug: Tolvaptan MR Drug: Tolvaptan IR Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 178 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind, Placebo-masked, Parallel-group Pilot Trial to Compare the Efficacy, Tolerability, and Safety of Tolvaptan Modified-release and Immediate-release Formulations in Subjects With Autosomal Dominant Polycystic Kidney Disease
Study Start Date : October 2011
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
Drug Information available for: Tolvaptan

Arm Intervention/treatment
Experimental: Tolvaptan MR 50 mg
Tolvaptan MR 50 mg capsule and 2 placebo IR tablets (AM) and 1 placebo IR tablet (PM)
Drug: Tolvaptan MR
50/80 mg capsules
Other Name: OPC-41061

Drug: Placebo

Experimental: Tolvaptan MR 80 mg
Tolvaptan MR 80 mg capsule and 2 placebo IR tablets (AM) and 1 placebo IR tablet (PM)
Drug: Tolvaptan MR
50/80 mg capsules
Other Name: OPC-41061

Drug: Placebo

Experimental: Tolvaptan IR 60/30 mg
Two tolvaptan IR 30-mg tablets and 1 placebo MR capsule (AM) and 1 tolvaptan IR 30-mg tablet (PM)
Drug: Tolvaptan IR
60/30 mg capsules
Other Name: OPC-41061

Drug: Placebo

Placebo Comparator: Placebo
Placebo MR capsule and 2 placebo IR tablets (AM) and 1 placebo IR tablet (PM)
Drug: Placebo

Primary Outcome Measures :
  1. Percent change in Total Kidney Volume (TKV) [ Time Frame: 3 weeks ]

Secondary Outcome Measures :
  1. Change in total score of the ADPKD-Urinary Impact Scale (UIS) [ Time Frame: 8 weeks ]
  2. Percent change in Total Kidney Volume (TKV) [ Time Frame: 8 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age 18 to 50
  2. Subjects with:

    • BMI between 19 and 35 kg/m2
    • diagnosis of ADPKD by modified Ravine criteria:

      • family history: 3cysts/kidney if by sonography or 5 by CT or MRI
      • Without family history: 10 cysts per kidney
    • an eGFR > 45 mL/min/1.73 m2 by the CKD-EPI equation
  3. Subjects not planning to become pregnant willing to comply with birth control requirements.
  4. Subjects must be in good health as determined by screening tests.
  5. Subjects providing informed consent and able to comply with all trial requirements.

Exclusion Criteria:

  1. Subjects using diuretics within 14 days prior to randomization, or the requirement for intermittent or constant diuretic use for any reason
  2. Subjects who had an eGFR < 45 mL/min/1.73 m2 calculated based on the most recent historical creatinine during the last 12 months
  3. Subjects with:

    • incontinence, overactive bladder, or urinary retention (eg, BPH), meaning subjects with symptoms of frequent nocturia, as determined by medical history or urinary urgency should be carefully evaluated to exclude non-ADPKD GU issues prior to entry.
    • liver disease, liver function abnormalities, or serology other than that expected for ADPKD with cystic liver disease at baseline
    • a history of renal surgery or cyst drainage within 6 months of randomization
    • blood pressure 150/95 mmHg or < 90/40 mmHg.
    • heart rate outside the range of 40 to 90 bpm.
    • advanced diabetes with a history of poor control, evidence of significant renal disease renal cancer, single kidney, or recent renal surgery
    • other significant medical history that may interfere with the study objectives
    • significant abnormalities in serum sodium concentration (< 135 or > 145 mEq/L)
    • a history of drug and/or alcohol abuse within 2 years prior to screening
    • clinically significant allergic reactions to tolvaptan or chemically related structures such as benzazepines (eg, benzazepril, conivaptan, fenoldopam mesylate, or mirtazapine)
  4. Subjects having taken an investigational drug within 30 days preceding randomization on Day 0
  5. Subjects taking medications or having concomitant illnesses likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting PKD cysts such as tolvaptan, somatostatin agonists (ie, octreotide, sandostatin), Rapamune (sirolimus), anti-sense RNA therapies, other vasopressin antagonists (eg, OPC-31260 [mozavaptan] and Vaprisol® [conivaptan]) or agonists (eg, desmopressin), and cyst reduction surgery
  6. Subjects on antihypertensives that have not been on the same antihypertensive regimen for at least 30 days prior to the first dose of IMP
  7. Subjects having contraindications to, or interference with, MRI assessments
  8. Subjects with a history of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial
  9. Subjects with previous exposure to tolvaptan

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01451827

  Hide Study Locations
United States, Alabama
Otsuka Investigational Site
Huntsville, Alabama, United States, 35802
Otsuka Investigational Site
Mobile, Alabama, United States, 36617
United States, Arizona
Otsuka Investigational Site
Peoria, Arizona, United States, 85381
Otsuka Investigational Site
Tempe, Arizona, United States, 85284
United States, California
Otsuka Investigational Site
Los Angeles, California, United States, 90025
Otsuka Investigational Site
San Diego, California, United States, 92108
United States, Colorado
Otsuka Investigational Site 2
Aurora, Colorado, United States, 80045
Otsuka Investigational Site
Aurora, Colorado, United States, 80045
Otsuka Investigational Site
Denver, Colorado, United States, 80210
United States, Connecticut
Otsuka Investigational Site
New Haven, Connecticut, United States, 06510
United States, Florida
Otsuka Investigational Site
Jacksonville, Florida, United States, 32216
Otsuka Investigational Site
Melbourne, Florida, United States, 32935
United States, Georgia
Otsuka Investigational Site
Atlanta, Georgia, United States, 30322
Otsuka Investigational Site
Augusta, Georgia, United States, 30901
United States, Illinois
Otsuka Investigational Site
Peoria, Illinois, United States, 61602
United States, Indiana
Otsuka Investigational Site
Mishawaka, Indiana, United States, 46545
United States, Kansas
Otsuka Investigational Site
Kansas City, Kansas, United States, 66160
United States, Kentucky
Otsuka Investigational Site
Paducah, Kentucky, United States, 42003
United States, Louisiana
Otsuka Investigational Site
Shreveport, Louisiana, United States, 71101
United States, Maryland
Otsuka Investigational Site
Baltimore, Maryland, United States, 21224
Otsuka Investigational Site
Rockville, Maryland, United States, 20850
United States, Massachusetts
Otsuka Investigational Site
Boston, Massachusetts, United States, 02111
United States, Michigan
Otsuka Investigational Site
Detroit, Michigan, United States, 48236
United States, Minnesota
Otsuka Investigational Site
Rochester, Minnesota, United States, 55905
United States, New Jersey
Otsuka Investigational Site
Voorhees, New Jersey, United States, 08043
United States, New York
Otsuka Investigational Site
Buffalo, New York, United States, 14215
United States, North Carolina
Otsuka Investigational Site
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Otsuka Investigational Site
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Otsuka Investigational Site
Bethleham, Pennsylvania, United States, 18017
Otsuka Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Otsuka Investigational Site
Anderson, South Carolina, United States, 29621
United States, Tennessee
Otsuka Investigational Site
Nashville, Tennessee, United States, 37205
United States, Texas
Otsuka Investigational Site
Arlington, Texas, United States, 76015
Otsuka Investigational Site
Mission, Texas, United States, 78572
United States, Virginia
Otsuka Investigational Site
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study Director: Frank Czerwiec, M.D., Ph.D. Otsuka Pharmaceutical Development & Commercialization, Inc.

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc. Identifier: NCT01451827     History of Changes
Other Study ID Numbers: 156-09-290
First Posted: October 14, 2011    Key Record Dates
Last Update Posted: June 19, 2014
Last Verified: June 2014

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Kidney Disease
Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease

Additional relevant MeSH terms:
Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs