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

NCT00550459 | Completed Phase 3 Results DMC

• 2 other identifiers: 156-04-246INSIGHT
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 12

Brief Summary

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

Conditions

Hyponatremia

Keywords

Hyponatremia; Cognitive; Neurological Function; Elderly

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores)

  Change from baseline to Day 22 in sum of all speed domain Z-scores:Reaction Time (Simple=recognize "yes" 50 times;Choice=recognize "yes" or "no" 50 times;Digit Vigilance=match 45 digits);Psychomotor Speed (Morse Tapping=tap button for 30 seconds with right \& left hands);Processing Speed (Rapid Visual Information Processing=detect consecutive sequences of 3 odd or 3 even digits;Numeric Working Memory=recognize numbers from series of 5 digits among 30;Word Recognition=remember 15 prior learned words from 30 total;results age-matched to healthy controls from Cognitive Drug Research normative data

  baseline and Day 22

Secondary Outcomes (28)

• Change From Baseline to Day 22 in the Individual Neurocognitive Domains Included in the Primary Endpoint: Reaction Time in Computer Tests

  baseline and Day 22

• Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Psychomotor Speed Via Morse Tapping Test

  baseline and Day 22

• Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Processing Speed of Rapid Visual Information Processing Test, Numeric Working Memory Test, and Word Recognition Test

  baseline and Day 22

• Change From Baseline in Overall Neurocognitive Composite Score

  baseline and Day 22

• Change From Baseline in Gait Test (Timed Get-Up-and-Go Test)

  baseline and Day 22

Study Arms (2)

1

PLACEBO COMPARATOR

Placebo tablet given once a day for 21 days

Drug: Placebo

2

ACTIVE COMPARATOR

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

Drug: Tolvaptan

Interventions

Tolvaptan DRUG

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

Also known as: OPC-41061

2

Placebo DRUG

Placebo tablet given once daily for 21 days

1

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator

Study Sites (12)

Sarah. S. Olelewe, MD

Hawthorne, California, 90250, United States

Location

Progressive Clinical Research

Vista, California, 92083, United States

Location

Pikes Peak Cardiology

Colorado Springs, Colorado, 80907, United States

Location

Innovative Research of West FL

Largo, Florida, 33770, United States

Location

Coastal Nephrology Assoc. Research Center

Punta Gorda, Florida, 33950, United States

Location

Rockdale Medical Research Associates

Conyers, Georgia, 30094, United States

Location

Otis Barnum, DO

Natchitoches, Louisiana, 71457, United States

Location

Lillestol Research, LLC

Fargo, North Dakota, 58106, United States

Location

Carolina Research Associates

Columbia, South Carolina, 29201, United States

Location

Wayne O. Wells, MD

Lebanon, Tennessee, 37087, United States

Location

Memorial Clinical Associates

Houston, Texas, 77043, United States

Location

Mitchell Rosner, MD

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Hyponatremia

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Pilot study powered only for serum Na+ improvements. Trial lacked sufficient power to detect changes in neurocognitive test scores and SF-12 and HDS outcomes.

Results Point of Contact

• Title: Frank Czerwiec, MD, PhD; Sr. Director, Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

frank.czerwiec@otsuka.com

(240) 683-3523

Study Officials

• Joseph Verbalis, MD

  Georgetown University, Washington, DC, 20007 USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 25, 2007
• First Posted: October 29, 2007
• Study Start: August 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: March 1, 2009
• Last Updated: April 28, 2011
• Results First Posted: April 28, 2011

Record last verified: 2011-04

Locations

US (12)