Bioavailability Study Comparing Tolvaptan Administered Via Nasogastric Tube to Tolvaptan Tablets Swallowed Intact

NCT01261481 | Completed Phase 1 DMC

• 1 other identifier: 10-1865
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to compare the relative bioavailability and pharmacokinetics of tolvaptan 15 mg tablets administered orally versus tolvaptan via nasogastric (NG) tube in healthy male and female subjects. This study is an open 2-treatment, 2-period, 2-sequence crossover study to compare the relative bioavailability of tolvaptan tablets to tolvaptan given via nasogastric tube in 28 healthy adults. Subjects will be randomized to one of the two treatment sequences; either tolvaptan oral tablets swallowed intact followed by a tablet crushed and administered via nasogastric tube, or the reverse sequence. Serial pharmacokinetic samples will be collected following each tolvaptan administration and safety assessments will be performed. The relative bioavailability of tolvaptan administered via nasogastric tube will be compared to tolvaptan tablets swallowed intact.

Conditions

Healthy

Keywords

Bioavailability

Outcome Measures

Primary Outcomes (4)

• Area under the plasma drug concentration-time curve from time 0 to infinity (AUC)

  PK samples: from pre-dose to 36 hours

• Area under the plasma drug concentration-time curve from time 0 to the last quantifiable point (AUC(0-t))

  PK samples: from pre-dose to 36 hours

• Maximum plasma concentration (Cmax)

  PK samples: from pre-dose to 36 hours

• Time to maximal concentration (Tmax)

  PK samples: pre-dose to 36 hours

Study Arms (2)

Tolvaptan Intact Tablet Orally

EXPERIMENTAL

Drug: Tolvaptan

Tolvaptan via Nasogastric Tube

EXPERIMENTAL

Drug: Tolvaptan

Interventions

Tolvaptan DRUG

Tolvaptan 15 mg administered once orally as an intact tablet.

Also known as: Samsca

Tolvaptan Intact Tablet Orally

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy - defined as being free from significant cardiac, pulmonary, gastrointestinal, hepatic, biliary, renal, hematological, neurological and psychiatric disease as determined by history, physical examination and clinical laboratory test results.
• Male or female between 18 and 40 years of age inclusive, at the time of signing the informed consent.
• A female is eligible to enter and participate in this study if she is of:
• i. Non-child bearing potential (i.e. postmenopausal, surgically sterile, bilateral tubal ligation, or oophorectomy); or
• ii. Child bearing potential, has a negative serum pregnancy test at screening, a negative urine pregnancy test on each admission day, and certifies compliance with one of the following:
• Complete abstinence from intercourse from 2 weeks prior to administration of the study drug, throughout the study, and 3 days after completion or premature discontinuation from the study to account for elimination of the study drug; or
• Sterilization of monogamous male partner; or
• Oral contraceptives if the subject has been taking them continuously for at least three months prior to the study; or
• Any FDA approved non-hormonal intrauterine device (IUD); or
• Within 20% of ideal body weight based on the subject's height (inches) and weight (kg).
• Willing and able to give written informed consent prior to entering the study.

You may not qualify if:

• Participated in another study within 30 days of the study period.
• A serum sodium less than 135 mEq/L at screening or on study days 1 or 8 of the study schedule.
• A positive urine or serum pregnancy test, or are currently breast-feeding.
• A history of intestinal surgery or gastrointestinal disorder that may affect drug absorption.
• Any clinically significant abnormal result on the screening blood tests, ECG, or physical exam.
• Use of CYP3A4 inhibitors or inducers as medications, juices, or herbal supplements within 96 hours prior to the study period.
• Use of oral or intravenous antibiotics within 14 days of the study period.
• A current history of alcohol or drug abuse.
• Any alcohol consumption within 24 h prior to study days 1 and 8 of the study schedule.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Otsuka America Pharmaceutical: collaborator

Study Sites (1)

University of North Carolina Healthcare

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Interventions

Tolvaptan

Intervention Hierarchy (Ancestors)

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

Study Officials

• J. Herbert Patterson, PharmD

  University of North Caronlina - Eshelman School of Pharmacy

  PRINCIPAL INVESTIGATOR

• Elizabeth B McNeely, PharmD

  University of North Caronlina - Eshelman School of Pharmacy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Executive Vice Chair, DPET

Study Record Dates

• First Submitted: December 14, 2010
• First Posted: December 16, 2010
• Study Start: January 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: February 1, 2012
• Last Updated: December 7, 2012

Record last verified: 2012-12

Locations

US (1)