Pharmacokinetic Comparisons of Two Donepezil Formulations

Phase 1

Completed

• Conditions: Alzheimer Disease
• Interventions: Drug: Donepezil, 10 mg tablet; Drug: Donepezil, ODT 10 mg

• Registration Number: NCT01297036
• Lead Sponsor: Korea University Anam Hospital

Brief Summary

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

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.

Study Timeline

• Status Verified: 2008-01
• Study Start: 2008-01
• Primary Completion: 2008-03
• Study Completion: 2008-05
• Study First Submitted: 2011-02-15
• Study First Submitted QC: 2011-02-15
• Last Update Submitted: 2011-02-15
• Study First Posted: 2011-02-16
• Last Update Posted: 2011-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 22

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Reference arm	Donepezil, 10 mg tablet	Treated with Reference (Aricept, 10 mg donepezil tablet)
Test arm	Donepezil, ODT 10 mg	Treated with Test (Neuropezil, 10 donepezil ODT, orally disintegrating tablet)

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Dept. of Clinical Pharmacology & Toxicology, Anam Hospital, Korea University College of Medicine; 🇰🇷 Seoul, Korea, Republic of