Three-way Crossover Study Comparing Ondansetron ODFS Administered With and Without Water to Zofran ODT Without Water

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: Drug: Ondansetron 8 mg ODFS without water; Drug: Ondansetron 8 mg ODFS with water; Drug: Zofran ODT (ondansetron 8 mg) without water

• Registration Number: NCT01220167
• Lead Sponsor: Aquestive Therapeutics

Brief Summary

This study conducted in healthy male and female adult participants compared the bioavailability and relative safety and tolerance of a single dose of ondansetron 8 mg Orally Dissolving Filmstrip (ODFS) administered under fasting conditions with and without water with that of a single dose of Zofran Orally Dissolving Tablets (ODT®) containing ondansetron 8 mg administered under fasting conditions without water.

Detailed Description

This was an open-label, single oral dose,randomized sequence, three-way crossover study to compare the bioavailability, safety and tolerability of ondansetron 8 mg Orally Dissolving Filmstrip (ODFS) administered without (Test Treatment A) and with water (Test Treatment B) with that of Zofran Orally Dissolving Tablets (ODT®) containing ondansetron 8 mg administered without water (Reference Treatment C) in healthy adult participants. The 3 treatment sequences were: ABC, BCA, and CAB, in which, all treatments were administered after an overnight fasting of at least 10 hours in each period.

Participants reported to the study site between 07:30 am to 04:30 pm on 22 Aug 2008, 25 Aug 2008, and 28 Aug 2008 for Period 1, Period 2, \& Period 3, respectively. Participants were served dinner between 8:00 pm to 8:30 pm, to ensure a minimum of 10 hours of fasting prior to administration of a single dose of either the test or reference product. Participants were dosed as per the randomization schedule with a 3-day wash out period between each administration.

A total of 18 blood samples (4 mL each) were collected from each subject in each period for pharmacokinetic analyses. Safety assessments including monitoring of adverse events, periodic physical examination, and vital signs monitoring. Urine Drug Screening was done at the time of check-in of all the study periods to identify participants with any substance abuse. Urine pregnancy screen (for female subjects only) was scheduled at the time of screening and at admission for Period 1, Period 2, Period 3. A clinical assessment, which included general and systemic examination, was done at the pre-study screening and post study physical examination. Clinical laboratory hematology and chemistry tests were performed at screening (pre-study) and at the study follow-up visit (post-study).

Study Timeline

• Study Start: 2008-08
• Primary Completion: 2008-08
• Study Completion: 2008-08
• Study First Submitted: 2010-10-12
• Study First Submitted QC: 2010-10-12
• Study First Posted: 2010-10-13
• Results First Submitted: 2011-07-25
• Status Verified: 2020-08
• Results First Submitted QC: 2020-08-06
• Last Update Submitted: 2020-08-06
• Results First Posted: 2020-08-18
• Last Update Posted: 2020-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

The criteria for inclusion in the study were:

• Study volunteer should provide written informed consent.
• Study volunteer must be a healthy adult within 18-45 years of age (inclusive).
• Study volunteer should have a Body mass index of ≥ 18.5 kg/m2 and ≤ 25 kg/m2, with body weight not less than 50 kg.
• Study volunteer should have a systolic blood pressure with upper limit of less than 140 mmHg and lower limit of more than or equal to 90 mm Hg.
• Study volunteer must be of normal health as determined by medical history and physical examination performed within 15 days prior to the dosing of period 1.
• Study volunteer should have a normal ECG, chest X-ray and vital signs.
• If study volunteer is a female and is of child bearing potential she must be practicing an acceptable method of birth control for the duration of the study.

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Exclusion Criteria

The criteria for exclusion from the study were:

• Study volunteer incapable of understanding the informed consent.
• Study volunteer with a history of hypersensitivity or idiosyncratic reaction to study drug or any other related drug.
• Study volunteer having any evidence of impairment of renal, hepatic, cardiac, lung or gastrointestinal function.
• Study volunteers with a history of tuberculosis, epilepsy, asthma (during past 5 years), diabetes, psychosis or glaucoma
• Study volunteer who smokes regularly more than ten cigarettes daily.
• Study volunteer who has taken over the counter or prescribed medications.
• Study volunteer with a history of any psychiatric illness, which may impair the ability to provide written, informed consent.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence BCA	Ondansetron 8 mg ODFS without water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment B (Ondansetron 8 mg ODFS with water), Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water), Test Treatment A (Ondansetron 8 mg ODFS without water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.
Sequence CAB	Ondansetron 8 mg ODFS with water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water), Test Treatment A (Ondansetron 8 mg ODFS without water), Test Treatment B (Ondansetron 8 mg ODFS with water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.
Sequence BCA	Ondansetron 8 mg ODFS with water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment B (Ondansetron 8 mg ODFS with water), Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water), Test Treatment A (Ondansetron 8 mg ODFS without water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.
Sequence CAB	Ondansetron 8 mg ODFS without water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water), Test Treatment A (Ondansetron 8 mg ODFS without water), Test Treatment B (Ondansetron 8 mg ODFS with water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.
Sequence ABC	Ondansetron 8 mg ODFS without water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment A (Ondansetron 8 mg ODFS without water), Test Treatment B (Ondansetron 8 mg ODFS with water), Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.
Sequence ABC	Zofran ODT (ondansetron 8 mg) without water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment A (Ondansetron 8 mg ODFS without water), Test Treatment B (Ondansetron 8 mg ODFS with water), Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.
Sequence CAB	Zofran ODT (ondansetron 8 mg) without water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water), Test Treatment A (Ondansetron 8 mg ODFS without water), Test Treatment B (Ondansetron 8 mg ODFS with water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.
Sequence BCA	Zofran ODT (ondansetron 8 mg) without water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment B (Ondansetron 8 mg ODFS with water), Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water), Test Treatment A (Ondansetron 8 mg ODFS without water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.
Sequence ABC	Ondansetron 8 mg ODFS with water	Six subjects received a single dose of each of the 3 study treatments in the following order: Test Treatment A (Ondansetron 8 mg ODFS without water), Test Treatment B (Ondansetron 8 mg ODFS with water), Test Treatment C (Zofran ODT® containing ondansetron 8 mg without water). Each dose was administered following a 10-hour fast with a 3-day washout period between doses.

Primary Outcome Measures

Name	Time	Method
Cmax	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose	Maximum Plasma Concentration (Time to reach maximum concentration)
AUCt	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose	Area Under Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (e.g., "0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose")
AUCinf	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose	Area Under Plasma Concentration-Time Curve From Time Zero to Time Infinity