A Study to Evaluate the Effect of Heat Application on the Delivery Profile of Corplex™ Donepezil Transdermal Delivery System (TDS)

Study Overview
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Brief Summary
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A study to assess the effect of heat application on the delivery profile of Corplex™ Donepezil Transdermal Delivery System (TDS)

Detailed Description
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2-Way Crossover study Approximately 24 healthy, adult male and female subjects will be enrolled. Subjects will be randomized to 1 of 2 treatment sequences prior to the first TDS application in treatment period 1. For each treatment period, subjects will have one 7-day TDS applied on their back. Depending on which sequence a subject is randomized to, the healthy subject will either be exposed to heat or not during the TDS wear time. Blood samples for Donepezil PK will be collected pre-dose until the end of each treatment period. Adhesion will be monitored throughout the TDS wear time, and skin irritation will be monitored after TDS removal. Subjects who complete the 2-way crossover study may be eligible to participate in the optional Study Extension Period. In the Study Extension Period, subjects will have their skin surface temperature monitored under the patch and adjacent to the TDS. Blood samples for Donepezil PK will not be collected, and adhesion will not be monitored for the Study Extension TDS wear period. Safety will be monitored throughout the study by adverse event reporting and repeated clinical and laboratory evaluations.

Official Title
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A Phase 1, 2-Way Crossover Study to Evaluate the Effect of Heat Application on the Delivery Profile of Corplex™ Donepezil 5 mg Transdermal Delivery System (TDS) in Healthy Volunteers

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 ≥ 30 years of age Exclusion Criteria: History of any illness that, in the opinion of the investigator, might confound the results of the study or poses an additional risk to the subject by participation in the study History or presence of alcoholism or drug abuse within the past 2 years prior to the first study product treatment History or presence of hypersensitivity or idiosyncratic reaction to the study products or related compounds History of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs History or presence of excessive sweating History or presence of hairy skin on application sites History or presence of significant skin damage or disease at application sites Any medical or surgical procedure or trauma within 28 days prior to the first study product treatment

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 |
| --- | --- |
| Other: Donepezil TDS with Heat Applied<br>Corplex Donepezil TDS 5 mg/day with heat applied | Drug: Donepezil TDS<br>* Donepezil Hydrochloride Transdermal Delivery System<br>|
| Other: Donepezil TDS without Heat<br>Corplex Donepezil TDS 5 mg/day with no heat applied | Drug: Donepezil TDS<br>* Donepezil Hydrochloride Transdermal Delivery System<br>|
| Other: Donepezil TDS Extension Study with Heat<br>Corplex Donepezil TDS 5 mg/day with heat. Two skin sensors will be placed underneath the TDS and adjacent to the TDS. | 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, Cmax | Peak plasma concentration (Cmax) of once-weekly Donepezil TDS in the presence and absence of heat | Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period, approximately 6 weeks total | 
| Pharmacokinetics, AUC | Area under the curve (AUC) of once-weekly Donepezil TDS in the presence and absence of heat | Blood samples for the Donepezil PK will be collected pre-dose until the end of each treatment period, approximately 6 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 and during the 5 week follow-on period | 
| Summary Listing of Skin Irritation Score of Donepezil 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 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 the presence and absence of heat | 0.5 hr, 24 hr, 48 hr, 72 hr after each TDS removal (3 days) | 
| Application Site Mean Adhesion Scores of Donepezil TDS | Adhesion data will be collected during each 7-day patch wear period | Daily during 1 week treatment period |