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

August 30, 2018 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

178

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tolvaptan MR 50 mg
Tolvaptan MR 50 mg capsule and 2 placebo IR tablets ( 8 AM) and 1 placebo IR tablet (4 PM) daily.
Drug: Tolvaptan MR
50/80 mg capsules
Other Names:
  • OPC-41061
Drug: Placebo
tablet
Experimental: Tolvaptan MR 80 mg
Tolvaptan MR 80 mg capsule and 2 placebo IR tablets (8 AM) and 1 placebo IR tablet (4 PM) daily.
Drug: Tolvaptan MR
50/80 mg capsules
Other Names:
  • OPC-41061
Drug: Placebo
tablet
Experimental: Tolvaptan IR 60/30 mg
Two tolvaptan IR 30-mg tablets and 1 placebo MR capsule (8 AM) and 1 tolvaptan IR 30-mg tablet (4 PM) daily.
Drug: Placebo
tablet
Drug: Tolvaptan IR
60/30 mg capsules
Other Names:
  • OPC-41061
Placebo Comparator: Placebo
Placebo MR capsule and 2 placebo IR tablets (8 AM) and 1 placebo IR tablet (4 PM) daily.
Drug: Placebo
tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Total Kidney Volume (TKV) at Week 3
Time Frame: Baseline to Week 3
The primary endpoint was percent change from baseline in TKV at Week 3. Total kidney volume is an important measure of disease progression. A 3-week time point is adequate to assess acute effects on kidney cyst shrinkage.
Baseline to Week 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Total Score of the Autosomal Dominant Polycystic Kidney Disease Urinary Impact Scale (ADPKD-UIS)
Time Frame: Baseline to Week 8
The ADPKD-UIS was a self-administered questionnaire designed to measure ADPKD-related urinary symptoms in participants with ADPKD. This instrument contained 11 items in 3 domains (Urinary Frequency, Urinary Urgency, and Nocturia). Each item was scored using a scale of 1 to 5 (a higher score indicated increased difficulty/extremely bothered). The maximum total score is 55; 1: not difficult/not bothered at all; 55: extremely difficult/extremely bothered.
Baseline to Week 8
Percent Change From Baseline in TKV at Week 8.
Time Frame: Baseline to Week 8
Total kidney volume is an important measure of disease progression. A 3-week time point is adequate to assess acute effects on kidney cyst shrinkage.
Baseline to Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

October 11, 2011

First Submitted That Met QC Criteria

October 13, 2011

First Posted (Estimate)

October 14, 2011

Study Record Updates

Last Update Posted (Actual)

September 27, 2018

Last Update Submitted That Met QC Criteria

August 30, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 156-09-290

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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