A Phase 1, Corplex™ Donepezil Transdermal System Compared to Oral Aricept®

Part A:

60 male and female subjects will be enrolled Subjects will receive 2 versions of once-weekly
Corplex Donepezil TDS and QD oral Aricept; each administered for 35 days in 3 different
treatment periods.

For each treatment period; Subjects will receive a lead-in dose of approximately 5 mg
donepezil/day for 7 days before commencing a dose of 10 mg donepezil/day for 28 days. Blood
samples for donepezil PK and red blood cell (RBC) AChEI (as a potential pharmacodynamic [PD]
marker) will be collected pre-dose through Week 8.

Adhesion and skin irritation will be monitored throughout TDS Treatments. A washout period of
at least 21 days between the last study drug administration (oral administration or removal
of TDS, as appropriate) in each treatment period and the first application of TDS or oral
drug administration, as appropriate, in the following treatment period.

Safety will be monitored throughout the study by adverse event reporting, repeated clinical
and laboratory evaluations

Part B:

Up to 47 subjects male and/or female will be enrolled This is an open-label, randomized,
2-way crossover sub-study. Eligible subjects will be randomized to 1 of 2 treatment sequences
prior to the first TDS application.

Subjects will receive 2 different once-weekly Corplex Donepezil TDS treatments (Treatments D
and E), each administered for 1 week, in 2 different treatment periods (Treatment Period 1
and Treatment Period 2).

In each treatment period, subjects will receive a target dose of 5 mg donepezil/day for 7
days. There will be a washout period of 35 days between removal of the first TDS in Treatment
Period 1 and application of the second TDS in Treatment Period 2.

Blood samples for donepezil PK will be collected pre-dose and through to Week 6 of each
treatment period.

Safety will be monitored throughout the sub-study by repeated clinical, skin irritation and
laboratory evaluations.

Inclusion Criteria:

- Healthy, adult, Caucasian, male or female ≥18 years of age at screening

- 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 60 days prior to the first
study drug administration

- Participation in another clinical study within 60 days prior to the first study drug
administration

- Clinically significant depression symptoms or suicidal ideation or behavior as
determined by the investigator: