Healthy Participants
Conditions
Keywords
bioavailability
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).
Interventions
DRUGOndansetron 8 mg ODFS without water
Single dose of Ondansetron 8 mg (ODFS) administered without water
DRUGOndansetron 8 mg ODFS with water
Single dose of Ondansetron 8 mg (ODSF) was orally administered, allowed to dissolve, swallowed with saliva, followed with water
DRUGZofran ODT (ondansetron 8 mg) without water
Single dose of Zofran ODT (containing ondansetron 8 mg) administered without water
Sponsors
Aquestive Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
Open label, balanced, randomized three period, three treatment, three sequence, three-way crossover bioavailability study .
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Participant flow
Recruitment details
Fifty-five healthy adult volunteers were screened for study eligibility between 18 Aug 2008 and 21 Aug 2008 at VIMTA VHS Research Centre in Adyar, Chennai - 600 113, India.
Pre-assignment details
Eighteen of 55 subjects were randomized. Of those not randomized, 29 did not meet eligibility criteria and 6 declined to participate. The 18 eligible participants reported to the study site on 22 Aug 2008, 25 Aug 2008 and 28 Aug 2008 for Period 1, Period 2, & Period 3, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Sequence ABC Each subject 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). | 6 |
| Sequence BCA Each subject 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). | 6 |
| Sequence CAB Each subject 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). | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 3 | Urine positive for substance abuse | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Sequence ABC | Sequence BCA | Sequence CAB | Total |
|---|---|---|---|---|
| Age, Continuous Age | 27.6 years STANDARD_DEVIATION 7.57 | 31.1 years STANDARD_DEVIATION 8.27 | 28.8 years STANDARD_DEVIATION 5.98 | 28.2 years STANDARD_DEVIATION 6.29 |
| Body Mass Index (kg/m^2 | 27.8 kg/m^2 STANDARD_DEVIATION 0.07 | 22.8 kg/m^2 STANDARD_DEVIATION 0.78 | 22.9 kg/m^2 STANDARD_DEVIATION 1.95 | 23.7 kg/m^2 STANDARD_DEVIATION 0.56 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 4 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
AUCinf
Area Under Plasma Concentration-Time Curve From Time Zero to Time Infinity
Time frame: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Population: 18 subject were enrolled. Only 17 completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ondansetron ODFS With or Without Water and Zofran ODT | AUCinf | ODFS without water | 311.349 ng*hr/mL | Standard Deviation 119.791 |
| Ondansetron ODFS With or Without Water and Zofran ODT | AUCinf | ODFS with water | 310.394 ng*hr/mL | Standard Deviation 112.7499 |
| Ondansetron ODFS With or Without Water and Zofran ODT | AUCinf | Zofran ODT | 306.497 ng*hr/mL | Standard Deviation 121.8256 |
Primary
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)
Time frame: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Population: 18 healthy subjects were enrolled. Only 17 subjects completed the study. 0 to 96 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ondansetron ODFS With or Without Water and Zofran ODT | AUCt | ODFS without water | 290.687 ng*hr/mL | Standard Deviation 106.5203 |
| Ondansetron ODFS With or Without Water and Zofran ODT | AUCt | ODFS with water | 291.069 ng*hr/mL | Standard Deviation 99.5911 |
| Ondansetron ODFS With or Without Water and Zofran ODT | AUCt | Zofran ODT | 285.457 ng*hr/mL | Standard Deviation 105.3048 |
Primary
Cmax
Maximum Plasma Concentration (Time to reach maximum concentration)
Time frame: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Population: 18 subjects were enrolled. One subject did not complete.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ondansetron ODFS With or Without Water and Zofran ODT | Cmax | Zofran ODT | 39.382 ng/mL | Standard Deviation 12.3572 |
| Ondansetron ODFS With or Without Water and Zofran ODT | Cmax | ODFS without water | 40.866 ng/mL | Standard Deviation 13.3089 |
| Ondansetron ODFS With or Without Water and Zofran ODT | Cmax | ODFS with water | 42.843 ng/mL | Standard Deviation 15.9103 |