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

NCT ID: NCT01451827

Last Updated: 2018-09-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

178 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2013-07-31

Brief Summary

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

Detailed Description

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Conditions

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Autosomal Dominant Polycystic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Tolvaptan MR 50 mg

Tolvaptan MR 50 mg capsule and 2 placebo IR tablets ( 8 AM) and 1 placebo IR tablet (4 PM) daily.

Group Type EXPERIMENTAL

Tolvaptan MR

Intervention Type DRUG

50/80 mg capsules

Placebo

Intervention Type DRUG

tablet

Tolvaptan MR 80 mg

Tolvaptan MR 80 mg capsule and 2 placebo IR tablets (8 AM) and 1 placebo IR tablet (4 PM) daily.

Group Type EXPERIMENTAL

Tolvaptan MR

Intervention Type DRUG

50/80 mg capsules

Placebo

Intervention Type DRUG

tablet

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.

Group Type EXPERIMENTAL

Tolvaptan IR

Intervention Type DRUG

60/30 mg capsules

Placebo

Intervention Type DRUG

tablet

Placebo

Placebo MR capsule and 2 placebo IR tablets (8 AM) and 1 placebo IR tablet (4 PM) daily.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

tablet

Interventions

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Tolvaptan MR

50/80 mg capsules

Intervention Type DRUG

Tolvaptan IR

60/30 mg capsules

Intervention Type DRUG

Placebo

tablet

Intervention Type DRUG

Other Intervention Names

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OPC-41061 OPC-41061

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Frank Czerwiec, M.D., Ph.D.

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

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Otsuka Investigational Site

Huntsville, Alabama, United States

Site Status

Otsuka Investigational Site

Mobile, Alabama, United States

Site Status

Otsuka Investigational Site

Peoria, Arizona, United States

Site Status

Otsuka Investigational Site

Tempe, Arizona, United States

Site Status

Otsuka Investigational Site

Los Angeles, California, United States

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Otsuka Investigational Site

San Diego, California, United States

Site Status

Otsuka Investigational Site 2

Aurora, Colorado, United States

Site Status

Otsuka Investigational Site

Aurora, Colorado, United States

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Otsuka Investigational Site

Denver, Colorado, United States

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Otsuka Investigational Site

New Haven, Connecticut, United States

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Otsuka Investigational Site

Jacksonville, Florida, United States

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Otsuka Investigational Site

Melbourne, Florida, United States

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Otsuka Investigational Site

Atlanta, Georgia, United States

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Otsuka Investigational Site

Augusta, Georgia, United States

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Otsuka Investigational Site

Peoria, Illinois, United States

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Otsuka Investigational Site

Mishawaka, Indiana, United States

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Otsuka Investigational Site

Kansas City, Kansas, United States

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Otsuka Investigational Site

Paducah, Kentucky, United States

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Otsuka Investigational Site

Shreveport, Louisiana, United States

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Otsuka Investigational Site

Baltimore, Maryland, United States

Site Status

Otsuka Investigational Site

Rockville, Maryland, United States

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Otsuka Investigational Site

Boston, Massachusetts, United States

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Otsuka Investigational Site

Detroit, Michigan, United States

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Otsuka Investigational Site

Rochester, Minnesota, United States

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Otsuka Investigational Site

Voorhees Township, New Jersey, United States

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Otsuka Investigational Site

Buffalo, New York, United States

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Otsuka Investigational Site

Chapel Hill, North Carolina, United States

Site Status

Otsuka Investigational Site

Cleveland, Ohio, United States

Site Status

Otsuka Investigational Site

Bethlehem, Pennsylvania, United States

Site Status

Otsuka Investigational Site

Philadelphia, Pennsylvania, United States

Site Status

Otsuka Investigational Site

Anderson, South Carolina, United States

Site Status

Otsuka Investigational Site

Nashville, Tennessee, United States

Site Status

Otsuka Investigational Site

Arlington, Texas, United States

Site Status

Otsuka Investigational Site

Mission, Texas, United States

Site Status

Otsuka Investigational Site

Charlottesville, Virginia, United States

Site Status

Countries

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United States

References

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St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Reference Type DERIVED
PMID: 39356039 (View on PubMed)

Other Identifiers

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156-09-290

Identifier Type: -

Identifier Source: org_study_id

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