A Clinical Study to Evaluate the Pharmacokinetics (PK) of Corplex™ Donepezil Transdermal Delivery System (TDS) Applied to Different Body Locations

Study Overview
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Brief Summary
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A Phase 1, Crossover Study to Evaluate the Pharmacokinetics of Corplex™ Donepezil 10 mg Transdermal Delivery System Applied to Different Body Locations

Detailed Description
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Randomized, open-label, 3-way crossover study Up to 66 healthy, adult male and female subjects will be enrolled. All subjects will receive Corplex Donepezil TDS patches applied to 3 different locations on each subject (back, buttock, and leg) during 3 different, consecutive treatment periods. For each subject, the location of product administration during each treatment period will be randomized. During each treatment period, all subjects will receive a once-weekly 10 mg TDS, target dose 10 mg donepezil/day, applied for 7 days (1 week) on either the back, buttock, or leg in accordance with the randomized treatment location for that treatment period. Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period. The PK sample collection time points are as follows: Week 1: Pre-TDS application prior to 0 hour and post-TDS application at 2, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 hours. Week 2: Pre-Week 1 TDS removal at 168 hours, and post-TDS removal at up to 528 hours 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 Phase 1, Crossover Study to Evaluate the Pharmacokinetics of Corplex™ Donepezil 10 mg Transdermal Delivery System Applied to Different Body Locations

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Donepezil TDS


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 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 Muscle relaxants, anti-Parkinsonian or neuroleptic medications prior to the first dose of study drug History or presence of significant skin damage or other skin disturbances as deemed by the Investigator to potentially interfere with patch procedures Use of donepezil hydrochloride or related drugs within 60 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 Back<br>Corplex Donepezil TDS 10 mg/day applied to the Back for 1 week (7 days) | Drug: Donepezil TDS<br>* Donepezil Hydrochloride Transdermal Delivery System<br>|
| Experimental: Donepezil TDS Buttock<br>Corplex Donepezil TDS 10 mg/day applied to the Buttock for 1 week (7 days) | Drug: Donepezil TDS<br>* Donepezil Hydrochloride Transdermal Delivery System<br>|
| Experimental: Donepezil TDS Leg<br>Corplex Donepezil TDS 10 mg/day applied to the Leg for 1 week (7 days) | Drug: Donepezil TDS<br>* Donepezil Hydrochloride Transdermal Delivery System<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics, AUC | Area under the plasma concentration versus time curve (AUC) of once-weekly Corplex Donepezil TDS applied to different body locations. | Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period, approximately 18 weeks total | 
| Pharmacokinetics, CMAX | Peak Plasma Concentration (Cmax) of once-weekly Corplex Donepezil TDS applied to different body locations. | Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period, approximately 18 weeks total | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | General Safety (adverse events and serious adverse events as reported by subject following guidance CTCAE v4.0) | Daily during 1 week treatment period throughout the 5 week period | 
| Summary Listing of Skin Irritation Score of Donepezil Corplex TDS by post-removal time point | Skin irritation score is determined by the sum of Dermal Response score (8-point categorical scale; where 0=no evidence of irritation to 7=strong reaction) using numeric values) and the Other Effects score (6-point categorical scale where 0=none observed to H=scabs/erosion using alphabet letters equivalent to numeric values) and summarized by application site (back, buttock and leg) | 0.5hr, 24hr, 48hr and 72hr after each TDS removal. (3 days) | 
| Application Site Mean Adhesion Scores of Donepezil Corplex TDS | Adhesion score is collected using a 12-point categorical scale, where 0=100% adhered to 11=detached | Daily during 1 week treatment period |