Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to evaluate the comparative bioavailability between granisetron hydrochloride 1 mg tablets (Teva Pharmaceuticals USA) and Kytril® 1 mg tablets (Roche, USA), after a single-dose in health subjects under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
2 x 1 mg, single dose fasting
2 x 1 mg, single dose fasting
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy, non-smoking, male and female subjects, 18 years of age or older. * BMI ≥ 19 and ≤ 30. * No significant diseases or clinically significant findings in a physical examination. * No clinically significant abnormal laboratory values. * No clinically significant findings in the 12-lead electrocardiogram (ECG). * No clinically significant findings from the vital signs measurement. * Be informed of the nature of the study and given written consent prior to receiving any study procedure. Negative for: * HIV. * Hepatitis B surface antigen and Hepatitis C antibody. * Urine drugs of abuse test (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone). * Urine cotinine test. * Serum HCG consistent with pregnancy (females only). Females who participate in this study are: * unable to have children (e.g. post-menopausal, tubal ligation, hysterectomy) OR * willing to remain abstinent \[not engage in sexual intercourse\] OR * willing to use an effective method of double-barrier birth control \[partner using condom and female using diaphragm, contraceptive sponge, spermicide or IUD\] * Females who participate in this study are not pregnant and/or non-lactating.
Exclusion criteria
* Known history or presence of any clinically significant medical condition. * Known or suspected carcinoma. * On a special diet within 4 weeks prior to drug administration (e.g. liquid, protein, raw food diet). * Participated in another clinical trial or received an investigational product within 30 days prior to drug administration. * Donated up to 250 mL of blood within the previous 30 days OR Donated from 251 to 500 mL of blood in the previous 45 days OR Donated more than 500 mL of blood in the previous 56 days (based on the Canadian Blood Services guideline for blood donation). * Females taking oral or transdermal hormonal contraceptives within 14 days preceding period 1 dosing OR females having taken implanted or injected hormonal contraceptives within 6 months prior to period 1 dosing. * Requirement of any non-topical medication (prescription and/or over-the-counter) on a routine basis. * Difficulty fasting or consuming the standard meals. * Do not tolerate venipuncture. * Unable to read or sign the ICF. Known history or presence of: * Hypersensitivity or idiosyncratic reaction to granisetron hydrochloride and/or any other drug substances with similar activity. * Alcoholism within the last 12 months. * Drug dependence and/or substance abuse. * Use of tobacco or nicotine-containing products, within the last 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration) | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| Auc0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] | Bl;ood samples collected over 36 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Granisetron (Test) First Granisetron 1 mg Tablet (test) dosed in first period followed by Kytril® 1 mg Tablet (reference) dosed in second period | 20 |
| Kytril® (Reference) First Kytril 1 mg Tablet (reference) dosed in first period followed by Granisetron 1 mg Tablet (test) dosed in second period | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
| First Intervention | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Granisetron (Test) First | Kytril® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 40 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants | 15 Participants | 32 Participants |
| Region of Enrollment Canada | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 21 Participants |
Outcome results
Primary
Auc0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)]
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Granisetron | Auc0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] | 148.5875 ng*h/mL | Standard Deviation 89.7077 |
| Kytril® | Auc0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] | 160.5850 ng*h/mL | Standard Deviation 99.0854 |
90% CI: [82.8, 103.48]
Primary
AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)]
Bioequivalence based on AUC0-t
Time frame: Bl;ood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Granisetron | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] | 145.4357 ng*h/mL | Standard Deviation 86.4059 |
| Kytril® | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] | 156.0218 ng*h/mL | Standard Deviation 93.5907 |
90% CI: [83.11, 103.97]
Primary
Cmax (Maximum Observed Concentration)
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Granisetron | Cmax (Maximum Observed Concentration) | 10.7738 ng/mL | Standard Deviation 3.1855 |
| Kytril® | Cmax (Maximum Observed Concentration) | 11.0935 ng/mL | Standard Deviation 3.4983 |
90% CI: [92.36, 103.69]