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

NCT01451827 | Completed Phase 2 Results

• 1 other identifier: 156-09-290
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 35

Brief Summary

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

Conditions

Autosomal Dominant Polycystic Kidney Disease

Keywords

Kidney Disease; Polycystic Kidney Disease; Autosomal Dominant Polycystic Kidney Disease; PKD; ADPKD

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Total Kidney Volume (TKV) at 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 Outcomes (2)

• Change From Baseline in Total Score of the Autosomal Dominant Polycystic Kidney Disease Urinary Impact Scale (ADPKD-UIS)

  Baseline to Week 8

• Percent Change From Baseline in TKV at Week 8.

  Baseline to Week 8

Study Arms (4)

Tolvaptan MR 50 mg

EXPERIMENTAL

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

Drug: Tolvaptan MR; Drug: Placebo

Tolvaptan MR 80 mg

EXPERIMENTAL

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

Drug: Tolvaptan MR; Drug: Placebo

Tolvaptan IR 60/30 mg

EXPERIMENTAL

Two tolvaptan IR 30-mg tablets and 1 placebo MR capsule (8 AM) and 1 tolvaptan IR 30-mg tablet (4 PM) daily.

Drug: Tolvaptan IR; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Tolvaptan MR DRUG

50/80 mg capsules

Also known as: OPC-41061

Tolvaptan MR 50 mg; Tolvaptan MR 80 mg

Tolvaptan IR DRUG

60/30 mg capsules

Also known as: OPC-41061

Tolvaptan IR 60/30 mg

Placebo DRUG

tablet

Placebo; Tolvaptan IR 60/30 mg; Tolvaptan MR 50 mg; Tolvaptan MR 80 mg

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 50
• 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
• Subjects not planning to become pregnant willing to comply with birth control requirements.
• Subjects must be in good health as determined by screening tests.
• Subjects providing informed consent and able to comply with all trial requirements.

You may not qualify if:

• Subjects using diuretics within 14 days prior to randomization, or the requirement for intermittent or constant diuretic use for any reason
• Subjects who had an eGFR \< 45 mL/min/1.73 m2 calculated based on the most recent historical creatinine during the last 12 months
• 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)
• Subjects having taken an investigational drug within 30 days preceding randomization on Day 0
• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (35)

Otsuka Investigational Site

Huntsville, Alabama, 35802, United States

Location

Otsuka Investigational Site

Mobile, Alabama, 36617, United States

Location

Otsuka Investigational Site

Peoria, Arizona, 85381, United States

Location

Otsuka Investigational Site

Tempe, Arizona, 85284, United States

Location

Otsuka Investigational Site

Los Angeles, California, 90025, United States

Location

Otsuka Investigational Site

San Diego, California, 92108, United States

Location

Otsuka Investigational Site 2

Aurora, Colorado, 80045, United States

Location

Otsuka Investigational Site

Aurora, Colorado, 80045, United States

Location

Otsuka Investigational Site

Denver, Colorado, 80210, United States

Location

Otsuka Investigational Site

New Haven, Connecticut, 06510, United States

Location

Otsuka Investigational Site

Jacksonville, Florida, 32216, United States

Location

Otsuka Investigational Site

Melbourne, Florida, 32935, United States

Location

Otsuka Investigational Site

Atlanta, Georgia, 30322, United States

Location

Otsuka Investigational Site

Augusta, Georgia, 30901, United States

Location

Otsuka Investigational Site

Peoria, Illinois, 61602, United States

Location

Otsuka Investigational Site

Mishawaka, Indiana, 46545, United States

Location

Otsuka Investigational Site

Kansas City, Kansas, 66160, United States

Location

Otsuka Investigational Site

Paducah, Kentucky, 42003, United States

Location

Otsuka Investigational Site

Shreveport, Louisiana, 71101, United States

Location

Otsuka Investigational Site

Baltimore, Maryland, 21224, United States

Location

Otsuka Investigational Site

Rockville, Maryland, 20850, United States

Location

Otsuka Investigational Site

Boston, Massachusetts, 02111, United States

Location

Otsuka Investigational Site

Detroit, Michigan, 48236, United States

Location

Otsuka Investigational Site

Rochester, Minnesota, 55905, United States

Location

Otsuka Investigational Site

Voorhees Township, New Jersey, 08043, United States

Location

Otsuka Investigational Site

Buffalo, New York, 14215, United States

Location

Otsuka Investigational Site

Chapel Hill, North Carolina, 27599, United States

Location

Otsuka Investigational Site

Cleveland, Ohio, 44106, United States

Location

Otsuka Investigational Site

Bethlehem, Pennsylvania, 18017, United States

Location

Otsuka Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Otsuka Investigational Site

Anderson, South Carolina, 29621, United States

Location

Otsuka Investigational Site

Nashville, Tennessee, 37205, United States

Location

Otsuka Investigational Site

Arlington, Texas, 76015, United States

Location

Otsuka Investigational Site

Mission, Texas, 78572, United States

Location

Otsuka Investigational Site

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• 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.

  PMID: 39356039 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Kidney Diseases; Polycystic Kidney Diseases

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Kidney Diseases, Cystic; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.

800 562-3974

Study Officials

• Frank Czerwiec, M.D., Ph.D.

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2011
• First Posted: October 14, 2011
• Study Start: October 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: September 27, 2018
• Results First Posted: August 13, 2018

Record last verified: 2018-08

Locations

US (35)