An Extension Follow-up Trial to Evaluate the Long-term Safety of Children and Adolescent Participants With Euvolemic or Hypervolemic Hyponatremia

NCT02020278 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 156-11-294
• Study Type: interventional
• Target: 3
• Locations: 8 countries
• Sites: 23

Brief Summary

The objective of this trial was to provide 6 months of safety follow-up for children and adolescents with dilutional (euvolemic or hypervolemic) hyponatremia who had previously participated in a tolvaptan hyponatremia trial and to assess the efficacy of tolvaptan in increasing serum sodium for those participants who received optional continuing tolvaptan treatment of variable duration (up to 6 months).

Conditions

Hyponatremia

Keywords

Hyponatremia; Euvolemic; Hypervolemic; Serum sodium; Dilutional hyponatremia; Electrolyte abnormality; Electrolyte imbalance; Metabolic disease; Water-Electrolyte Imbalance

Outcome Measures

Primary Outcomes (1)

• Change From Baseline At Month 6 In Serum Sodium While Tolvaptan Was Being Administered

  No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected for this outcome measure.

  Baseline, Month 6

Secondary Outcomes (13)

• Percentage Of Participants Who Required Rescue Therapy While On Tolvaptan Treatment

  Month 6

• Percentage Of Participants Who Had Recurrence Of Hyponatremia While On Tolvaptan

  Month 6

• Percentage Of Participants Requiring Continuation Of Tolvaptan Following 30 Days Of Treatment

  Month 6

• Change From Baseline In Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Total Score At Month 6

  Baseline, Month 6

• Change From Baseline In PedsQL GCS Physical Health Summary Score At Month 6

  Baseline, Month 6

Study Arms (1)

Tolvaptan

EXPERIMENTAL

Participants enrolled in this trial were eligible to receive open-label tolvaptan if they had a clinical need as determined by the investigator and met the eligibility criteria for optional tolvaptan treatment. Daily dose levels would have included 3.75 milligrams (mg), 7.5 mg, 15 mg, 30 mg, and 60 mg.

Drug: Tolvaptan

Interventions

Tolvaptan DRUG

Tolvaptan 3.75-, 7.5-, 15-, and 30-mg spray-dried tablets. Dosage: Depending on age and weight, Tablet (3.75 mg - 60 mg daily). Frequency: Once daily. Duration: Participants may be eligible to receive short-term or long-term optional tolvaptan treatment at any time during their participation in the trial, with one or more treatment cycles over a 6-month period.

Also known as: SAMSCA®

Tolvaptan

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• Optional Tolvaptan Treatment Component (per treatment cycle)
• Eligibility Criteria:
• Male and female participants ≥ 4 years of age (or per local Health Authority age restrictions) and ≥ 10 kilograms (kg).
• Participant must have been off treatment with the investigational medicinal product for at least 7 days following the end of treatment in the previous tolvaptan trial for hyponatremia (euvolemic or hypervolemic).
• Persistent dilutional (euvolemic or hypervolemic) hyponatremia defined as being documented as present for at least 48 hours, evidenced by at least 2 serum sodium assessments \< 130 milliequivalents (mEq)/liter (L) (millimole \[mmol\]/L) drawn at least 12 hours apart (these values can be documented using historical values previously obtained per standard of care); a third (STAT) serum sodium assessment \< 130 mEq/L (mmol/L), which will serve as the baseline value for efficacy endpoints, had to be obtained within 2 to 4 hours prior to the first dose of tolvaptan.
• Ability to swallow tablets.
• Ability to maintain adequate fluid intake whether orally or via intravenous support with adequate monitoring.
• Ability to comply with all requirements of the trial.
• Trial-specific written informed consent/assent obtained from a parent/legal guardian or legally acceptable representative, as applicable per age of participant or local laws, prior to the initiation of any protocol-required procedures. In addition, the participant as required by local laws must provide informed assent at the pretreatment baseline for this trial and must be able to understand that he or she can withdraw from the trial at any time. All informed consent/assent procedures must be in accordance with the trial center's Institutional Review Board/Independent Ethics Committee and local regulatory requirements.
• Ability to commit to remain fully abstinent (periodic abstinence \[for example, calendar, ovulation, symptothermal, post-ovulation methods\] or withdrawal are not acceptable methods of contraception) or practice double-barrier birth control during the trial and for 30 days following the last dose of IMP for sexually active females of childbearing potential.
• Ineligibility Criteria:
• Had evidence of hypovolemia or intravascular volume depletion (for example, hypotension, clinical evidence of volume depletion, response to saline challenge); if the participant had systolic blood pressure or heart rate outside of the normal range for that age, then volume status was to be specifically clinically assessed to rule out volume depletion.
• Had serum sodium \< 120 mEq/L (mmol/L), with or without associated neurologic impairment (that is, symptoms such as apathy, confusion, or seizures).
• Use of potent CYP3A4 inhibitors in participants ≤ 50 kg or moderate CYP3A4 inhibitors in participants \< 20 kg.
• Lacked free access to water (inability to respond to thirst) or without ICU-level fluid monitoring and management.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• Syneos Health: collaborator

Study Sites (23)

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Washington D.C., District of Columbia, 20010, United States

Location

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Atlanta, Georgia, 30322, United States

Location

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Grand Rapids, Michigan, 49503, United States

Location

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Kansas City, Missouri, 64108, United States

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New York, New York, 10032, United States

Location

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Stony Brook, New York, 11794-8111, United States

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The Bronx, New York, 10467, United States

Location

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Cleveland, Ohio, 44106, United States

Location

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Philadelphia, Pennsylvania, 19104, United States

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Seattle, Washington, 98105, United States

Location

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Ghent, 9000, Belgium

Location

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Prague, 5 150 06, Czechia

Location

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Erlangen, Nurnberg, Germany

Location

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Leipzig, Saxony, 04289, Germany

Location

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Genova, 16147, Italy

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Naples, 80131, Italy

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Palermo, 90134, Italy

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Rome, 00165, Italy

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Bucharest, 022238, Romania

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Sibiu, 550166, Romania

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Madrid, 28007, Spain

Location

Unknown Facility

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Hyponatremia; Metabolic Diseases; Water-Electrolyte Imbalance

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

This trial was prematurely terminated due to challenges in enrollment. The trial was not terminated due to safety reasons. Due to early termination of the study, no efficacy data were collected.

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: December 24, 2013
• Study Start: April 22, 2016
• Primary Completion: October 23, 2017
• Study Completion: October 23, 2017
• Last Updated: April 17, 2020
• Results First Posted: April 17, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); CZ (1); DE (2); ES (1); IT (4); BE (1); GB (1); RO (2)