Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
This study compared the relative bioavailability (rate and extent of absorption) of 90 mg Fluoxetine Hydrochloride Capsules by Teva Pharmaceuticals, USA with that of 90 mg PROZAC WEEKLY® Capsules by Eli Lilly and Company following a single oral dose (1 x 90 mg) in healthy adult volunteers under non-fasting conditions.
Interventions
90 mg Capsules
DRUGPROZAC WEEKLY®
90 mg Capsules
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Screening Demographics: All volunteers selected for this study will be healthy men or women 18 years or age or older at the time of dosing. The weight range will not exceed + 15% for height and body frame as per Desirable Weights for Men - 1983 Metropolitan Height and Weight Table or as per Desirable Weights for Women - 1983 Metropolitan Height and Weight Table. * Screening Procedures: Each volunteer will complete the screening process within 28 days prior to Period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures. * If female and: * Of childbearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), or * Is postmenopausal for at least 1 year, or * Is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).
Exclusion criteria
* Volunteers with a recent history of drug or alcohol addiction or abuse. * Volunteers with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurological system(s) or psychiatric disease (as determined by the clinical investigators). * Volunteers whose clinical laboratory test values are outside the acceptable reference range and when confirmed on re-examination are deemed to be clinically significant. * Volunteers demonstrating a positive hepatitis B surface antigen screen or a reactive HIV antibody screen. * Volunteers demonstrating a positive drug abuse screen when screened for this study. * Female volunteers demonstrating a positive pregnancy screen. * Female volunteers who are currently breastfeeding. * Volunteers with a history of allergic response(s) to fluoxetine or related drugs. * Volunteers with a history of clinically significant allergies including drug allergies. * Volunteers with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators). * Volunteers who currently use tobacco products. * Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to Period I dosing. * Volunteers who report donating greater than 150 mL of blood within 30 days prior to Period I dosing. All subjects will be advised not to donate blood for 4 weeks after completing the study. * Volunteers who have donated plasma within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for 4 weeks after completing the study. * Volunteers who report receiving any investigational drug within 30 days prior to Period I dosing. * Volunteers who report taking any systemic prescription medications in the 14 days prior to Period I dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Fluoxetine. | Blood samples collected over a 25 day period. | Bioequivalence based on Fluoxetine Cmax (maximum observed concentration of drug substance in plasma). |
| AUC0-t of Fluoxetine. | Blood samples collected over a 25 day period. | Bioequivalence based on Fluoxetine AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration). |
| AUC0-inf of Fluoxetine. | Blood samples collected over a 25 day period. | Bioequivalence based on Fluoxetine AUC0-inf (area under the concentration-time curve from time zero to infinity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Norfluoxetine. | Blood samples collected over a 25 day period. | Informational comparison of Cmax values for the metabolite Norfluoxetine. |
| AUC0-t of Norfluoxetine. | Blood samples collected over a 25 day period. | Informational comparison of AUC0-t values for the metabolite Norfluoxetine. |
| AUC0-inf of Norfluoxetine. | Blood samples collected over a 25 day period. | Informational comparison of AUC0-inf values for the metabolite Norfluoxetine. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluoxetine Hydrochloride (Test) First 90 mg Fluoxetine Hydrochloride Capsules test product dosed in first period followed by 90 mg Prozac® Weekly Capsules reference product dosed in the second period. | 13 |
| Prozac® Weekly (Reference) First 90 mg Prozac® Weekly Capsules reference product dosed in first period followed by 90 mg Fluoxetine Hydrochloride Capsules test product dosed in the second period. | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Fluoxetine Hydrochloride (Test) First | Prozac® Weekly (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 | 13 Participants | 13 Participants | 26 Participants |
| Race/Ethnicity, Customized Caucasian | 13 participants | 13 participants | 26 participants |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 26 | 11 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 |
Outcome results
Primary
AUC0-inf of Fluoxetine.
Bioequivalence based on Fluoxetine AUC0-inf (area under the concentration-time curve from time zero to infinity).
Time frame: Blood samples collected over a 25 day period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine Hydrochloride (Test) | AUC0-inf of Fluoxetine. | 4432.21 ng*h/mL | Standard Deviation 1591 |
| Prozac® Weekly (Reference) | AUC0-inf of Fluoxetine. | 4398.46 ng*h/mL | Standard Deviation 1277 |
90% CI: [93.53, 108.56]
Primary
AUC0-t of Fluoxetine.
Bioequivalence based on Fluoxetine AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).
Time frame: Blood samples collected over a 25 day period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine Hydrochloride (Test) | AUC0-t of Fluoxetine. | 4148.71 ng*h/mL | Standard Deviation 719 |
| Prozac® Weekly (Reference) | AUC0-t of Fluoxetine. | 4120.11 ng*h/mL | Standard Deviation 614.1 |
90% CI: [92.9, 109.14]
Primary
Cmax of Fluoxetine.
Bioequivalence based on Fluoxetine Cmax (maximum observed concentration of drug substance in plasma).
Time frame: Blood samples collected over a 25 day period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine Hydrochloride (Test) | Cmax of Fluoxetine. | 75.32 ng/mL | Standard Deviation 14.7 |
| Prozac® Weekly (Reference) | Cmax of Fluoxetine. | 69.86 ng/mL | Standard Deviation 14.9 |
90% CI: [97.37, 119.38]
Secondary
AUC0-inf of Norfluoxetine.
Informational comparison of AUC0-inf values for the metabolite Norfluoxetine.
Time frame: Blood samples collected over a 25 day period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine Hydrochloride (Test) | AUC0-inf of Norfluoxetine. | 13505.84 ng*h/mL | Standard Deviation 5234 |
| Prozac® Weekly (Reference) | AUC0-inf of Norfluoxetine. | 13365.13 ng*h/mL | Standard Deviation 6325 |
90% CI: [94.76, 107.77]
Secondary
AUC0-t of Norfluoxetine.
Informational comparison of AUC0-t values for the metabolite Norfluoxetine.
Time frame: Blood samples collected over a 25 day period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine Hydrochloride (Test) | AUC0-t of Norfluoxetine. | 114575.21 ng*h/mL | Standard Deviation 3451 |
| Prozac® Weekly (Reference) | AUC0-t of Norfluoxetine. | 10849.08 ng*h/mL | Standard Deviation 2978 |
90% CI: [99.97, 111.56]
Secondary
Cmax of Norfluoxetine.
Informational comparison of Cmax values for the metabolite Norfluoxetine.
Time frame: Blood samples collected over a 25 day period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine Hydrochloride (Test) | Cmax of Norfluoxetine. | 35.11 ng/mL | Standard Deviation 12.6 |
| Prozac® Weekly (Reference) | Cmax of Norfluoxetine. | 33.47 ng/mL | Standard Deviation 13.1 |
90% CI: [98.53, 111.64]