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

Open-label, Randomized, Three-way Crossover Bioavailability Study Comparing Ondansetron Orally Dissolving Filmstrip (ODFS) With and Without Water to Zofran Orally Dissolving Tablets (ODT) Without Water in Healthy Adult Study Participants

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Ondansetron 8 mg ODFS without water; Drug: Ondansetron 8 mg ODFS with water; Drug: Zofran ODT (ondansetron 8 mg) 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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence ABC; 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.	Drug: Ondansetron 8 mg ODFS without water; Single dose of Ondansetron 8 mg (ODFS) administered without water; Other Names: Test Treatment (A); Drug: Ondansetron 8 mg ODFS with water; Single dose of Ondansetron 8 mg (ODSF) was orally administered, allowed to dissolve, swallowed with saliva, followed with water; Other Names: Test Treatment (B); Drug: Zofran ODT (ondansetron 8 mg) without water; Single dose of Zofran ODT (containing ondansetron 8 mg) administered without water; Other Names: Reference Treatment (C)
Experimental: Sequence BCA; 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.	Drug: Ondansetron 8 mg ODFS without water; Single dose of Ondansetron 8 mg (ODFS) administered without water; Other Names: Test Treatment (A); Drug: Ondansetron 8 mg ODFS with water; Single dose of Ondansetron 8 mg (ODSF) was orally administered, allowed to dissolve, swallowed with saliva, followed with water; Other Names: Test Treatment (B); Drug: Zofran ODT (ondansetron 8 mg) without water; Single dose of Zofran ODT (containing ondansetron 8 mg) administered without water; Other Names: Reference Treatment (C)
Experimental: Sequence CAB; 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.	Drug: Ondansetron 8 mg ODFS without water; Single dose of Ondansetron 8 mg (ODFS) administered without water; Other Names: Test Treatment (A); Drug: Ondansetron 8 mg ODFS with water; Single dose of Ondansetron 8 mg (ODSF) was orally administered, allowed to dissolve, swallowed with saliva, followed with water; Other Names: Test Treatment (B); Drug: Zofran ODT (ondansetron 8 mg) without water; Single dose of Zofran ODT (containing ondansetron 8 mg) administered without water; Other Names: Reference Treatment (C)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum Plasma Concentration (Time to reach maximum concentration)	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
AUCt	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")	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
AUCinf	Area Under Plasma Concentration-Time Curve From Time Zero to Time Infinity	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose

Collaborators and Investigators

• Sponsor: Aquestive Therapeutics
• Investigators: Principal Investigator: Sudershan Vishwanath, MD, Vimta Labs Ltd.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: October 12, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 13, 2010

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: bioavailability
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Ondansetron
• Other Study ID Numbers: OND/CR/051/08/09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No