Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients

NCT ID: NCT00550459

Last Updated: 2011-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2009-03-31

Brief Summary

Demonstrate an improvement in the composite scores of validated neurocognitive tests in elderly subjects with chronic sub-clinical (i.e., asymptomatic) hyponatremia.

Detailed Description

Subjects will be randomized, with stratification by baseline sodium <130 or ≥ 130 mEq/L[mmol/L] to receive either tolvaptan 15 mg tablet or matching placebo tablet at doses of 15, 30 or 60 mg for 21 days. During this period, fluid restrictions should be loosened or suspended, until the subject's response to therapy can be evaluated, typically over the first few days of therapy. Fluid restriction may be reinstituted at any time in subjects whose sodium fails to improve or worsens with study therapy. A forced-titration up to 60 mg of study drug by day 3 to 7 will be based on the subject's serum sodium Subjects entering the study with a serum sodium concentration less than 130 mEq/L[mmol/L] may be fluid restricted if necessary at the discretion of the Investigator. Subjects should be monitored closely during the first 24 hours of treatment for dosing titration. The total dosing duration will be up to 21 days (plus 3 day treatment window). Subjects will return to the clinic on Day 22 (+3 days) for assessments and will complete a follow-up visit on Day 28 (+2 days).

Conditions

Hyponatremia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Placebo tablet given once a day for 21 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablet given once daily for 21 days

2

Tolvaptan 15 mg-60 mg tablet given once a day for 21 days.

Group Type: ACTIVE_COMPARATOR

Tolvaptan

Intervention Type: DRUG

15-60 mg oral tablet given once a day for 21 days.

Interventions

Tolvaptan

15-60 mg oral tablet given once a day for 21 days.

Intervention Type: DRUG

Placebo

Placebo tablet given once daily for 21 days

Intervention Type: DRUG

Other Intervention Names

OPC-41061

Eligibility Criteria

Inclusion Criteria

• Women and men 50 years of age or older.
• Serum Sodium ≥123 and ≤ 134 mEq/L [mmol/L]at screening and baseline.
• Subjects with serum sodium concentrations ≥118 and ≤122 mEq/L[mmol/L] at screening and baseline may be entered into the trial based on consultation and approval from the study medical monitor.

Exclusion Criteria

• Conditions or history which may present a safety concern to the subject or their offspring or extreme susceptibility to hypotension with sudden fluid loss (aquaresis).
• Hyponatremia that is acute, easily reversible, artifactual, or due to a condition not associated with vasopressin excess or likely to respond to aquaretic therapy.
• Conditions associated with an independent imminent risk of morbidity and mortality.
• Conditions which may confound the assessment of endpoints, history of poor compliance, participation in a clinical trial believed by the PI or Sponsor likely to confound endpoint assessments.
• Conditions which may confound primary endpoints of cognitive function.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Otsuka Pharmaceutical Development & Commercialization, Inc.

Principal Investigators

Joseph Verbalis, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown University, Washington, DC, 20007 USA

Locations

Sarah. S. Olelewe, MD

Hawthorne, California, United States

Progressive Clinical Research

Vista, California, United States

Pikes Peak Cardiology

Colorado Springs, Colorado, United States

Innovative Research of West FL

Largo, Florida, United States

Coastal Nephrology Assoc. Research Center

Punta Gorda, Florida, United States

Rockdale Medical Research Associates

Conyers, Georgia, United States

Otis Barnum, DO

Natchitoches, Louisiana, United States

Lillestol Research, LLC

Fargo, North Dakota, United States

Carolina Research Associates

Columbia, South Carolina, United States

Wayne O. Wells, MD

Lebanon, Tennessee, United States

Memorial Clinical Associates

Houston, Texas, United States

Mitchell Rosner, MD

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

INSIGHT

Identifier Type: -

Identifier Source: secondary_id

156-04-246

Identifier Type: -

Identifier Source: org_study_id