Pharmacokinetic Comparisons of Two Donepezil Formulations

Study Overview
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Brief Summary
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To compare the relative bioavailability and pharmacokinetic characteristics of a newly developed donepezil formulation with a conventional formulation in healthy subjects with a single dose, randomized, open-label, 2-sequence -2period crossover study.

Detailed Description
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This single dose, open label, balanced, randomized, two-treatment, two-period, two-sequence, crossover study was conducted to compare the relative bioavailability and pharmacokinetic characteristics of a newly developed formulation with a conventional formulation in healthy subjects. For this, a single-center, randomized, single-dose, open-label, 2-way crossover study with a 21-day washout period was conducted in 22 healthy volunteers. Plasma samples for the analysis of donepezil were collected up to 240 h after drug administration. Participants received either reference or test drug formulation of 10 mg donepezil in the first period and the alternative formulation in the second period. Plasma concentrations of donepezil were determined by validated high-performance liquid chromatography coupled to tandem mass spectrometry detection. Pharmacokinetic parameters, including Cmax and AUC, were determined by noncompartmental analysis. Analysis of variance (ANOVA) was carried out using log-transformed Cmax and AUC, and the mean ratios and their 90% confidence intervals (CI) were calculated. According to regulatory requirements set forth by Korea and the US Food and Drug Administration, products meet the criteria for bioequivalence if the 90% CIs of the mean ratios for Cmax and AUC are within the range of 0.80 to 1.25.

Official Title
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Open Label, Randomized, Single-dose, Crossover Study to Evaluate the Pharmacokinetic Characteristics of Donepezil Between Two Donepezil Products, Aricept® Tablet and Neuropezil ODT, in Healthy Subjects

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Donepezil, ODT 10 mg
* Drug: Donepezil, 10 mg tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males age 20 to 45 years Body weight > 45 kg with +/- 20% of ideal body weight Signed and dated informed consent form which meets all criteria of current FDA and KFDA regulations Exclusion Criteria: subjects with acute conditions. presence of history affecting ADME Clinically significant history or current evidence of a hepatic, renal, gastrointestinal, or hematologic abnormality Hepatitis B, hepatitis C, or HIV infection revealed on the laboratory findings Any other acute or chronic disease A history of hypersensitivity to donepezil A history of alcohol or drug abuse Participation in another clinical trial within 3 months smoked >10 cigarettes daily consumption over 5 glasses daily of beverages containing xanthine derivatives use of any medication having the potential to affect the study results within 10 days before the start of the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reference arm<br>Treated with Reference (Aricept, 10 mg donepezil tablet) | Drug: Donepezil, 10 mg tablet<br>* Reference: Donepezil Hydrochloride 10 mg Tablet<br>* Other names: Manufactured by Dae Woong harm. Co. Ltd, Seoul, Korea;|
| Experimental: Test arm<br>Treated with Test (Neuropezil, 10 donepezil ODT, orally disintegrating tablet) | Drug: Donepezil, ODT 10 mg<br>* Test- Donepezil Hydrochloride 10 mg Tablet single dose<br>* Other names: developed by Chong Kun Dang Co, Ltd.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| donepezil pharmacokinetics: peak plasma concentrations (Cmax) |  | 240 hours | 
| donepezil pharmacokinetics: Area under the time vs. plasma concentration curve from 0 to 240 hr(AUCall) |  | 240 hours | 
| donepezil pharmacokinetics: Area under the time vs. plasma concentration curve from 0 to infinity(AUCinf) |  | 240 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Bioequivalence, Donepezil