Clinical trial NCT01297036: Pharmacokinetic Comparisons of Two Donepezil Formulations
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Keywords: Pharmacokinetics
Bioequivalence
Donepezil
Lead sponsor: Korea University Anam Hospital
Sponsor class: OTHER
Collaborators: name: Chong Kun Dang Pharmaceutical Corp.
First posted: 2011-02-16
Enrollment: 22
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: donepezil pharmacokinetics: peak plasma concentrations (Cmax)
timeFrame: 240 hours
measure: donepezil pharmacokinetics: Area under the time vs. plasma concentration curve from 0 to 240 hr(AUCall)
timeFrame: 240 hours
measure: donepezil pharmacokinetics: Area under the time vs. plasma concentration curve from 0 to infinity(AUCinf)
timeFrame: 240 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Dept. of Clinical Pharmacology & Toxicology, Anam Hospital, Korea University College of Medicine
Study officials:
affiliation: Anam Hospital, Korea Univeristy College of Medicine
name: Ji-Young Park, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim KA, Lim JL, Kim C, Park JY. Pharmacokinetic comparison of orally disintegrating and conventional donepezil formulations in healthy Korean male subjects: a single-dose, randomized, open-label, 2-sequence, 2-period crossover study. Clin Ther. 2011 Jul;33(7):965-72. doi: 10.1016/j.clinthera.2011.06.003. Epub 2011 Jul 2.