Nausea and Vomiting, Postoperative, Nausea With Vomiting Chemotherapy-Induced
Conditions
Keywords
Bioequivalence, safety, and tolerability
Brief summary
This was an open-label, balanced, two-treatment, two-period, randomized sequence crossover bioequivalence study with a 7-day washout between periods. Each treatment was administered after an overnight (10 hours) fast.
Detailed description
This was an open label, balanced, randomized, two-treatment, two-period, randomized sequence crossover study conducted in healthy adult male and female volunteers. Subjects checked into the study center on Day -1 of each study period at least 12 hours prior to dosing on Day 1. Subjects were served dinner between 8:00 pm to 8:30 pm to ensure minimum 10 hours fast prior to dosing in both periods. Subjects received the 2 treatments in a randomized order with a 7-day washout between the 2 periods. Treatment A: single dose of ondansetron ODFS 8 mg was orally administered, allowed to dissolve, swallowed with saliva, followed with 240 mL room temperature drinking water Treatment B: single dose of Zofran ODT (containing ondansetron 8 mg) was orally administered, allowed to dissolve, swallowed with saliva, followed with 240 mL room temperature drinking water
Interventions
Test Article
DRUGZofran (ODT)
Comparator
Sponsors
MonoSol Rx
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
Two period study, two treatment, randomized sequence
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Volunteer should have written informed consent. * Volunteer healthy adult within 18-45 years of age (inclusive). * Body mass index of 18.5 kg/m\^2 and 25 kg/m\^2, body weight not less than 50 kg. * Volunteer must be of normal health. * Volunteer should have a normal ECG, chest X-ray and vital signs. * If study volunteer is a female and is of child bearing potential practicing an acceptable method of birth control for the duration of the study. Criteria:
Exclusion criteria
* Volunteer doesn't understand the informed consent. * Volunteer with a history of hypersensitivity or idiosyncratic reaction to study drug or any other related drug. * Volunteer having any evidence of impairment of renal, hepatic, cardiac, lung or gastrointestinal function, by standard laboratory, imaging or monitoring procedures * Volunteer who smokes regularly, alcohol or drug abuse * Volunteer who has taken over the counter or prescribed medications * Volunteer with clinically significant abnormal values of laboratory parameters. * Volunteer who has participated in any other clinical investigation using experimental drug or had bled more than 350 mL in the past 3 months. * Female volunteer demonstrating a positive pregnancy screen with urine pregnancy test (strip method).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 0,0.33,0.67,1,1.33,1.67,2,2.33,2.67,3,4,6,8,10,12,15,18,24 hours | Maximum Plasma Concentration occurring at Tmax (Time to reach maximum concentration) |
| AUCt | 0,0.33,0.67,1,1.33,1.67,2,2.33,2.67,3,4,6,8,10,12,15,18,24 hours | Area Under Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration |
| AUCinf | 0,0.33,0.67,1,1.33,1.67,2,2.33,2.67,3,4,6,8,10,12,15,18,24 hours | Area Under Plasma Concentration-Time Curve From Time Zero to Time Infinity |
Countries
India
Participant flow
Recruitment details
The planned sample size was 48. Of the 48 participants enroll in the study, 46 completed the study.
Pre-assignment details
A total of 68 volunteers (52 males and 16 females) were screened for enrollment and a total of 48 volunteers (41 males and 7 females) were subsequently admitted to the study.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Ondansetron ODFS, Then Zofran ODT 24 participants completed treatment with Ondansetron ODSF 8 mg. After a washout period of 7 days, 24 of the 24 participants who completed the first treatment also completed treatment with Zofran ODT 8mg. | 24 |
| Experimental: Zofran ODT, Then Ondansetron ODFS 24 participants completed treatment with Zofran ODT 8 mg. After a washout period of 7 days, 22 of the 24 participants who completed the first treatment also completed treatment with Ondansetron ODSF 8 mg | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Dosing | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Experimental: Ondansetron ODFS, Then Zofran ODT | Experimental: Zofran ODT, Then Ondansetron ODFS | Total |
|---|---|---|---|
| Age, Continuous Age | 29.7 years STANDARD_DEVIATION 6.08 | 28.7 years STANDARD_DEVIATION 5.6 | 29.2 years STANDARD_DEVIATION 0.7 |
| Region of Enrollment India | 24 Participants | 24 Participants | 48 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 20 Participants | 21 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 22 |
| other Total, other adverse events | 6 / 24 | 7 / 22 |
| serious Total, serious adverse events | 0 / 24 | 0 / 22 |
Outcome results
Primary
AUCinf
Area Under Plasma Concentration-Time Curve From Time Zero to Time Infinity
Time frame: 0,0.33,0.67,1,1.33,1.67,2,2.33,2.67,3,4,6,8,10,12,15,18,24 hours
Population: 46 subjects completed both periods. 2 subjects did not complete period 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ondansetron ODFS | AUCinf | 225.032 nghr/mL | Standard Deviation 88.2551 |
| Zofran ODT | AUCinf | 250.673 nghr/mL | Standard Deviation 107.9654 |
Primary
AUCt
Area Under Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration
Time frame: 0,0.33,0.67,1,1.33,1.67,2,2.33,2.67,3,4,6,8,10,12,15,18,24 hours
Population: 46 subjects completed both Treatments. 2 subjects did not return for Period 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ondansetron ODFS | AUCt | 216.269 ng*hr/mL | Standard Deviation 83.2883 |
| Zofran ODT | AUCt | 239.463 ng*hr/mL | Standard Deviation 100.0745 |
Primary
Cmax
Maximum Plasma Concentration occurring at Tmax (Time to reach maximum concentration)
Time frame: 0,0.33,0.67,1,1.33,1.67,2,2.33,2.67,3,4,6,8,10,12,15,18,24 hours
Population: Pharmacokinetic analysis population comprised all subjects who received study drug in both study periods and completed the study. Two of the 24 subjects in the Zofran ODT then Ondansetron ODSF arm did not return for Period 2 for personal reasons other than adverse events (voluntary withdrawal).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ondansetron ODFS | Cmax | 37.282 ng/mL | Standard Deviation 14.9177 |
| Zofran ODT | Cmax | 41.108 ng/mL | Standard Deviation 17.2442 |