Healthy
Conditions
Keywords
Healthy Subjects, Bioequivalence
Brief summary
The objective of this study is to evaluate the comparative bioavailability between Anastrozole 1 mg Tablets (Teva Pharmaceuticals USA) and Arimidex® 1 mg Tablets (AstraZeneca Pharmaceuticals LP, USA), after a single-dose in healthy subjects under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods
Interventions
DRUGAnastrozole (Teva Pharmaceuticals USA)
1 mg Tablets
DRUGAnastrozole (Arimidex®)
1 mg Tablets
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy, non-smoking, post-menopausal or surgically sterile female subjects 18 years or age or older. * Body mass index (BMI) between 19 and 30, inclusive. * Indicate non-child bearing status by one of the following criteria: * Indication of successful hysterectomy. * No spontaneous menses for at least 1 year, must have luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels within postmenopausal range. * Indication of successful bilateral oophorectomy. * 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 pregnancy test. * 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. * Participants in this study will be unable to have children (i.e. post-menopausal, hysterectomy).
Exclusion criteria
* Known history or presence of any clinically significant medical condition. * Known or suspected carcinoma. * Known history of: * Hypersensitivity or idiosyncratic reaction to anastrozole 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. * Taken any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to dosing. * Taken any hormone replacement therapy (HRT) for 4 weeks prior to dosing. * 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. * 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 informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Anastrozole(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 72 hour period. | Bioequivalence based on Anastrozole Cmax. |
| AUC0-t of Anastrozole(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 72 hour period. | Bioequivalence based on Anastrozole AUC0-t. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anastrazole (Test) First 1 mg Anastrozole Tablets test product dosed in first period followed by 1 mg Arimidex® Tablets reference product dosed in the second period. | 11 |
| Arimidex® (Reference) First 1 mg Arimidex® Tablets reference product dosed in first period followed by 1 mg Anastrazole Tablets test product dosed in the second period. | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
| Washout of 21 Days | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Anastrazole (Test) First | Arimidex® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 11 Participants | 21 Participants |
| Race/Ethnicity, Customized Black | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 10 participants | 11 participants | 21 participants |
| Region of Enrollment Canada | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 22 | 4 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
AUC0-t of Anastrozole(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Bioequivalence based on Anastrozole AUC0-t.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anastrazole (Test) | AUC0-t of Anastrozole(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 503 ng*h/mL | Standard Deviation 110 |
| Arimidex® (Reference) | AUC0-t of Anastrozole(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 519 ng*h/mL | Standard Deviation 94 |
90% CI: [93.14, 99.57]
Primary
Cmax of Anastrozole(Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Anastrozole Cmax.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anastrazole (Test) | Cmax of Anastrozole(Maximum Observed Concentration of Drug Substance in Plasma) | 17.1 ng/mL | Standard Deviation 3.3 |
| Arimidex® (Reference) | Cmax of Anastrozole(Maximum Observed Concentration of Drug Substance in Plasma) | 17.8 ng/mL | Standard Deviation 2.7 |
90% CI: [92.34, 98.95]