A Phase I Clinical Study, Randomized, Single-blind, Placebo-controlled, Multiple Doses, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of Donepezil Patch in Healthy Male Subjects.

Study Overview
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Brief Summary
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Study of the Safety, tolerability and pharmacokinetics with multiple doses of donepezil patch in healthy male subjects

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Donepezil
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI : more than 19 ㎏/㎡, less than 27 ㎏/㎡ Systolic blood pressure : more than 90, less than 140 (mmHg) Diastolic blood pressure : more than 60, less than 100 (mmHg) Exclusion Criteria: Evidence of clinically significant, severe, active, or unstable gastrointestinal, renal,hepatic, respiratory, hematological, endocrine, or cardiovascular system disease. A history of skin disease or skin graft Hypersensitivity to donepezil or piperidine derivatives or any of the excipients. A known or suspected history of drug or alcohol dependency or abuse Patients who have participated in another clinical study within 60 days. Whole blood within 60 days, apheresis within 30 days, transfusion within 30 days Heavy alcohol intake(more than 21 units/week) Heavy smoker(more than 10 cigarette/day) Abnormal clinical laboratory values which are judged clinically significant by the investigator. Any condition that would make the patient or the caregiver, in the opinion of the investigator, unsuitable for 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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dosage 1<br>drug : 9 people(87.5mg/25cm2) placebo : 3 people(0mg/25cm2) | Drug: Donepezil<br> <br> Drug: placebo<br> <br> |
| Experimental: dosage 2<br>dosage2 period 1 : oral administration drug : 12 people(10mg) dosage 2 period 2: transdermal administration drug : 9 people(175mg/50cm2) placebo : 3 people(0mg/50cm2) | Drug: Donepezil<br> <br> Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability evaluation | evaluation item adverse event electrocardiographie vital sign physical examination urine, blood test skin irritation | patch : -1d 33d, oral : -1 11d | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics characteristic evaluation | cohort 1 1d 0h (pre-dose), 4h, 8h, 12h, 24h (2d), 48h (3d), 72h (4d), 144h (7d), 216h (10d), 288h (13d, last dose start), 292h, 296h, 300h, 312h (14d), 336h (15d), 360h (16d, patch removal), 362h, 364h, 368h, 372h, 384h (17d), 408h (18d), 432h (19d), 480h (21d), 528h (23d), 576h (25d) cohort 2 1 period Oral Donepezil 1d 0h (pre-dose), 0.5h, 1h, 1.5h, 2h, 3h, 4h, 8h, 12h, 24h (2d), 48h (3d), 96h (5d), 144h (7d), 192h (9d), 240h (11d) period 2 Donepezil Patch: same cohort1 evaluation item : donepezil conc. evaluation variable patch : AUCτ,ss, Cmax,ss, t1/2β, AI (accumulation index), Cav,ss oral : AUClast, AUC0-∞, Cmax, tmax, t1/2β, CL/F | patch: -1 25d, oral -1 11d |