Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
This study investigated the relative bioavailability (rate and extent of absorption) of Donepezil Hydrochloride Orally Disintegrating Tablets, 10 mg by Teva Pharmaceuticals, USA with that of Aricept® Orally Disintegrating Tablets, Manufactured and Marketed by Eisai Inc., following a single oral dose (1 x 10 mg orally disintegrating tablet) in healthy adult subjects administered under fasting conditions.
Interventions
DRUGDonepezil Hydrochloride
10 mg Orally Disintegrating Tablet
DRUGAricept®
10 mg Orally Disintegrating Tablet
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
SINGLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Screening Demographics: All volunteers for this study will be healthy men and women 18 years of age or older at the time of dosing. The weight range will not exceed + 20% for height and body frame as per Desirable Weights for Adults-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.
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 neurologic system(s) or psychiatric disease (as determined by the clinical investigators). * Volunteers whose clinical laboratory test values are outside the accepted reference range and when confirmed on reexamination are deemed to be clinically significant. * Volunteers demonstrating a reactive screen for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody. * 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 donepezil 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 28 days prior to Period I dosing. * Volunteers who report donating greater than 150 mL of blood within the 28 days prior to Period I dosing. * Volunteers who have donated plasma within 14 days prior to Period I dosing. * Volunteers who report receiving any investigational drug within 28 days prior to Period I dosing. * Volunteers who report taking any systemic prescription medication in the 14 days prior to Period I dosing. * Female volunteers who report the use of oral contraceptives or injectable contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Donepezil. | Blood samples collected over a 72 hour period. | Bioequivalence based on Donepezil Cmax (maximum observed concentration of drug substance in plasma). |
| AUC0-t of Donepezil. | Blood samples collected over a 72 hour period. | Bioequivalence based on Donepezil AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Donepezil Hydrochloride (Test) First 10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in first period followed by 10 mg Aricept® Orally Disintegrating Tablets reference product dosed in the second period. | 13 |
| Aricept® (Reference) First 10 mg Aricept® Orally Disintegrating Tablets reference product dosed in first period followed by 10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in the second period. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Withdrawal by Subject | 0 | 1 |
| Second Intervention | Emesis | 0 | 2 |
| Washout of 28 Days | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Donepezil Hydrochloride (Test) First | Aricept® (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 | 12 participants | 13 participants | 25 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 26 | 6 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 |
Outcome results
Primary
AUC0-t of Donepezil.
Bioequivalence based on Donepezil AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).
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 |
|---|---|---|---|
| Donepezil Hydrochloride (Test) | AUC0-t of Donepezil. | 466307.49 ng*h/mL | Standard Deviation 85094.55 |
| Aricept® (Reference) | AUC0-t of Donepezil. | 490716.21 ng*h/mL | Standard Deviation 86199.11 |
90% CI: [92.11, 97.46]
Primary
Cmax of Donepezil.
Bioequivalence based on Donepezil Cmax (maximum observed concentration of drug substance in plasma).
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 |
|---|---|---|---|
| Donepezil Hydrochloride (Test) | Cmax of Donepezil. | 17800.27 ng/mL | Standard Deviation 4515.36 |
| Aricept® (Reference) | Cmax of Donepezil. | 17280.23 ng/mL | Standard Deviation 4032.57 |
90% CI: [97.07, 107.51]