A Bioequivalence Study of Corplex™ Donepezil Transdermal Delivery System Compared to Aricept®

Study Overview
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Brief Summary
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A study to assess the steady-state bioequivalence of once-weekly Corplex™ Donepezil 10 mg Transdermal Delivery System (TDS) compared to daily administration of Aricept®

Detailed Description
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Open label, randomized, 2-period, multiple-dose crossover study. Approximately 86 healthy, adult male and female subjects will be enrolled. Subjects will be randomized to 1 of 2 treatment sequences prior to the first study product treatment in treatment period 1. For each treatment period; subjects will receive donepezil for 5 consecutive weeks. Blood samples for donepezil PK will be collected pre-dose through week 10. Adhesion and skin irritation will be monitored throughout TDS treatments. Safety will be monitored throughout the study by adverse event reporting, repeated clinical and laboratory evaluations.

Official Title
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A Study to Assess the Steady-State Bioequivalence of Once-Weekly Corplex™ 10mg Donepezil Transdermal Delivery System Compared to Daily Oral Administration of Aricept®

Conditions
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Alzheimer's Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, adult, male or female Body mass index ≥ 18.0 and ≤ 32.0 kg/m2 at screening Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECGs), as deemed by the Investigator Have a Fitzpatrick skin type of I, II or III or have skin colorimeter scores equivalent to the allowed Fitzpatrick skin type Key Exclusion Criteria: History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (including piperidine derivatives and other cholinesterase inhibitors) Has intolerance to venipuncture and/or inability to comply with the extensive blood sampling required for this study or does not have suitable veins in both arms Potential for occupational exposure to anticholinesterase agents. Female subjects with a positive pregnancy test or lactating Positive urine drug or alcohol results Estimated creatinine clearance in non-elderly subjects <80 mL/min at screening and in elderly subjects (i.e., ≥55 years of age) <60 mL/min at screening Hemoglobin value of less than 11.5 g/dl for females, 13.0 g/dl for males at screening and first check-in Any of the following drugs for 28 days prior to the first dose of study drug in Treatment Period 1 and throughout the study: significant inducers of cytochrome P450 (CYP) enzymes and/or P-glycoprotein; anti-inflammatory drugs or cyclooxygenase 2 (COX-2) analgesic; beta-blockers; anti-fungal medications; anti-histamines; cholinergics and anti-cholinergics; oral corticosteroids; Prolia; adjuvant analgesics Muscle relaxants, anti-Parkinsonian or neuroleptic medications prior to the first dose of study drug History or presence of excessive hairy skin on application sites as deemed by the Investigator to potentially interfere with 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 irritation assessments Use of donepezil hydrochloride or related drugs within 30 days prior to the first study drug administration Participation in another clinical study within 30 days prior to the first study drug administration Clinically significant depression symptoms or suicidal ideation or behavior as determined by the Investigator

Ages Eligible for Study
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Minimum Age: 30 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil TDS<br>Corplex Donepezil TDS 5 mg/day followed by Donepezil TDS 10mg/day applied weekly for 5 consecutive weeks | Drug: Donepezil TDS<br>* Donepezil Hydrochloride Transdermal Delivery System<br>|
| Active Comparator: Aricept<br>Aricept 5 mg/day followed by Aricept 10 mg/day once daily for 5 consecutive weeks | Drug: Aricept<br>* Aricept Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK, AUC | To assess the plasma concentration (AUC) of once-weekly Corplex Donepezil (TDS) compared to once-daily (QD) administration of Aricept (donepezil hydrochloride [HCl]). | Blood samples for donepezil PK will be collected pre dose until the end of each treatment period, approximately 10 weeks total | 
| PK, Cmax | To assess the maximum observed concentrations (Cmax) of once-weekly Corplex Donepezil (TDS) compared to once-daily (QD) administration of Aricept (donepezil hydrochloride [HCl]). | Blood samples for donepezil PK will be collected pre dose until the end of each treatment period, approximately 10 weeks total | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PI assessment of local skin irritation response to TDS | To evaluate the safety and tolerability (including local skin irritation) of once-weekly Corplex Donepezil TDS. Dermal Response assessed using 8 point categorical scale. Other effects assessed using a 6 point scale. | 0.5hr, 24hr, 48hr and 72hr after each TDS removal. (5 consecutive weeks) | 
| PI assessment of TDS Adhesion | Adhesion data will be collected during each 7-day patch wear period throughout 5 week treatment period. Percent adherence will be assessed using 12 point categorical scale. | Daily during 5 week treatment period | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | General Safety (AE and SAE as reported by subject following guidance CTCAE v4.0) | Daily during 5 week treatment period and during the 5 week follow-on period |