Crossover Pharmacokinetic (PK) Study of 5 and 10 mg Corplex™ Donepezil TDS Compared to 10 mg Aricept® in Healthy Volunteers

Study Overview
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Brief Summary
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Phase 1, open-label, randomized, 3-period, 3-treatment, crossover pharmacokinetic study to evaluate the steady-state pharmacokinetics of 5 mg/day and 10 mg/day Corplex™ Donepezil TDS manufactured with the commercial process compared to 10 mg Aricept® in healthy volunteers.

Detailed Description
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Screening Period: Subjects will undergo a Screening Period up to 28 days prior to entering the Treatment Phase. Treatment Phase consisting of 3 Treatment periods with 3 Treatments A, B, C. Treatment Period 1: All Subjects will receive Treatment A; 5 mg/day Donepezil Transdermal Delivery System (TDS); 1-week wear and applied for 5 consecutive weeks. Treatment Periods 2 and 3: Subjects will be randomized (by gender) to receive either sequences of Treatments B-C or Treatments C-B. Treatment B: 10 mg/day Donepezil TDS 1-week wear and applied weekly for 5 consecutive weeks Treatment C: 10 mg/day Aricept® donepezil tablet administered daily (QD) for 5 weeks. Blood samples for pharmacokinetics and safety assessments will be collected during the Treatment Phase.

Official Title
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A Phase 1, Open-Label, 3-Period, Randomized, Crossover Pharmacokinetic Study to Evaluate the Steady-State Pharmacokinetics of 5 mg and 10 mg Corplex™ Donepezil Transdermal Delivery Systems Compared to 10 mg Oral Administration of Aricept® in Healthy Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Combination Product: Donepezil TDS
* Drug: Aricept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females. Subject's Body Mass Index (BMI) must be between 18 and 32 kg/m2 (inclusive). Subject must be continuous non-smokers. Subject must have a Fitzpatrick skin type of I, II or III. Exclusion Criteria: History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results. After resting seated for at least 3 minutes, subjects should be excluded from the study with the following vital signs at Screening systolic blood pressure outside the range of 90-145 mmHg, or diastolic blood pressure outside the range of 50-90 mmHg, or resting heart rate outside the range of 40-100 beats per minute. Has an isolated ALT ≥1.5x the ULN or AST ≥1.5x the ULN at Screening; or both ALT and AST exceeding the ULN. Estimated creatinine clearance at screening <70 mL/min/1.73 m2. Prolonged corrected QTcF on screening ECG (≥450 ms for both females and males). History or presence of excessive hairy skin on application sites as deemed by the Investigator to potentially interfere with patch adhesion or drug absorption. History or presence of significant skin damage, diffuse skin diseases-, scars, tattoos on the application sites or other skin disturbances as deemed by the Investigator to potentially interfere with drug absorption or skin tolerability assessments Use of donepezil hydrochloride or related drugs within 60 days prior to the first study drug administration. Has participated in another clinical trial within 30 days prior to Day -1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Phase 1, open-label, randomized, 3-period, 3-treatment, crossover PK study to evaluate the steady-state pharmacokinetics
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>5 mg/day Donepezil Transdermal Delivery System (TDS) 1-week wear and applied weekly for 5 consecutive weeks | Combination Product: Donepezil TDS<br>* Transdermal Delivery System<br>|
| Experimental: Treatment B<br>10 mg/day Donepezil TDS 1-week wear and applied weekly for 5 consecutive weeks | Combination Product: Donepezil TDS<br>* Transdermal Delivery System<br>|
| Active Comparator: Treatment C<br>10 mg/day Aricept® donepezil tablet administered QD for 5 consecutive weeks | Drug: Aricept<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steady State Bioequivalence of 10 mg/day donepezil | To evaluate steady-state donepezil plasma exposure following once-weekly treatments with 10 mg/day Corplex™ Donepezil TDS compared to once-daily oral administration of 10 mg Aricept® | 35 days of Treatment of each comparator | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donepezil, Transdermal Delivery System