Study in Elderly Alzheimer's Patients to Assess Skin Tolerability, Irritation With 3, 7-Day Applications of DTP-System

Study Overview
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Brief Summary
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This study is designed to assess skin tolerability, skin irritation, and adhesion of the 350 mg Donepezil Transdermal Patch (DTP-system), following 3, 7-day applications to 3 specific areas of the body (upper back, upper middle arm, side of torso) of elderly Alzheimer's patients. The total application time for the DTP-system is 21 days.

Detailed Description
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This is a randomized, placebo-controlled study designed to evaluate skin irritation, skin tolerability, and adhesion of the 350 mg DTP-system following 3 consecutive 7-day applications to 3 specific areas of the body (upper back, upper arm, side of torso) of elderly Alzheimer's patients. The total exposure time for the DTP-system is 21 days. All patients receive 1 Donepezil Transdermal Patch (DTP-system) and 1 placebo patch, each applied to opposite sides of the body (e.g., placebo patch to the left side of the upper back, and DTP-system to the right side of the upper back). Patients are randomized to receive the active patch to either the left or the right side of the body according to 1 of 6 treatment sequences listed below. The treatment sequence is repeated for the opposite side of the body for a total of 12 treatment sequences (4 patients in each treatment sequence). The patches are applied to one of 3 body locations for 7 days, for a total exposure period of 21 days, according to one of the following sequences: Upper Back, Upper Arm, Side of Torso (Right) Upper Arm, Side of Torso, Upper Back (Right) Side of Torso, Upper Back, Upper Arm (Right) Upper Back, Side of Torso, Upper Arm (Right) Upper Arm, Upper Back, Side of Torso (Right) Side of Torso, Upper Arm, Upper Back (Right) Upper Back, Upper Arm, Side of Torso (Left) Upper Arm, Side of Torso, Upper Back (Left) Side of Torso, Upper Back, Upper Arm (Left) Upper Back, Side of Torso, Upper Arm (Left) Upper Arm, Upper Back, Side of Torso (Left) Side of Torso, Upper Arm, Upper Back (Left) Patches are applied on Days 1, 8, and 15 according to the randomization schedule. Oral Aricept is taken daily through Day -1, and is re-started on Day 22 or at the time of early termination if before Day 22. Patients are seen in the clinic at Screening and on Days 1, 8, 15, 22, and at the End of Study Visit; for all other daily visits, the patients may be seen either at the clinic or in their residence, provided the assessments are completed as described in the protocol. Skin irritation is assessed immediately upon patch removal and at 1, 24, and 48 hours after removal.

Official Title
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Randomized, Placebo-Controlled Study in Elderly Alzheimer's Patients on Established/Well Tolerated Dose of Aricept to Assess Skin Tolerability, Irritation, Adhesion With 3 Consecutive 7-Day Applications of 350 mg Donepezil Transdermal Patch

Conditions
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Irritation/Irritant

Intervention / Treatment
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* Drug: 350 mg Donepezil Transdermal Patch
* Drug: Placebo Patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female at least 65 years of age. Established dose of Aricept 10 mg at least 2 months prior to enrollment. Established diagnosis of stable Alzheimer's disease treated with oral Aricept Must be willing to change from oral Aricept to DTP (and placebo patch). Body mass index of at least 18 and a minimum weight of at least 45 kg. Blood pressure (sitting) must be diastolic <95mmHg, and systolic <145, stable for at least 3 months. Patients with well-controlled hypertension (with medication) may enroll as long as 3-month stability criterion is met. Those with stable cardiac disease may be enrolled provided the patient has been on appropriate medication for 3 months prior to screening. Those with a pacemaker may be enrolled. Pulse rate between 45 - 100 bpm; respirations between 8 - 20 per minute. Those with thyroid disease may enroll if stable on treatment for at least 3 months prior to screening, and maintain the same dose of thyroid medication throughout the study. Must have a caregiver who is either living with the patient or is in daily contact with the patient, agrees to be present at all visits, provide information as required, and ensure compliance with the medication schedule. Free from any abnormality at Screening which may compromise the patient's ability to participate. Free of any dermatologic conditions, excessive hair or skin allergies and sensitivities. Male patients who have female partners of childbearing potential must use a condom. Must understand and provide written informed consent (or have a Legally Authorized Representative who is able), prior to the initiation of any protocol-specific procedures. Must be willing and able to abide by all study requirements and restrictions. Must be on stable medications for at least 30 days prior to enrollment into the study. Exclusion Criteria: Use of systemic or topical antihistamines within 72 hours prior to enrollment, or systemic or topical corticosteroids within 3 weeks of study enrollment or foreseen use during the study. History of allergy to Donepezil hydrochloride or to piperidine derivatives, related drugs, or any of the drug excipients or other drug product components. Those with a recent (< 2 years) cancer (except for non-melanoma skin cancers, females with in-situ cancer of the cervix or males with localized prostate cancer requiring no treatment). Presence of history of a psychiatric disorder, or other seizure disorder deemed clinically significant. Those with a known plan for elective surgery during the study period. Those taking antidepressant medication. Abnormality (e.g., scar, tattoo) or unhealthy skin (e.g., burns, wounds) at the application site; or an existing chronic skin disease or history of skin disease at the application site(s) within the 30 days prior to enrollment. Treatment with any investigational drug within 30 days prior to enrollment in the study. Any condition which would make the patient or caregiver, in the opinion of the investigator or designee, not suitable for the study for any reason. Current or pending legal charges that may affect patient or caregiver compliance. Treatment with medications contraindicated for use with Aricept

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upper Back<br>350 mg Donepezil Transdermal Patch (active) and placebo patch, each applied to opposite sides of the upper back. | Drug: 350 mg Donepezil Transdermal Patch<br>* Active and placebo patches will be applied to opposite sides for 7 days.<br>Drug: Placebo Patch<br>* Active and placebo patches will be applied to opposite sides for 7 days.<br>|
| Experimental: Upper Arm<br>350 mg Donepezil Transdermal Patch (active) and placebo patch, each applied to opposite arms. | Drug: 350 mg Donepezil Transdermal Patch<br>* Active and placebo patches will be applied to opposite sides for 7 days.<br>Drug: Placebo Patch<br>* Active and placebo patches will be applied to opposite sides for 7 days.<br>|
| Experimental: Side of Torso<br>350 mg Donepezil Transdermal Patch (active) and placebo patch, each applied to opposite sides of torso. | Drug: 350 mg Donepezil Transdermal Patch<br>* Active and placebo patches will be applied to opposite sides for 7 days.<br>Drug: Placebo Patch<br>* Active and placebo patches will be applied to opposite sides for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin Irritation (Erythema and Edema) | Erythema and edema were used to determine skin irritation using a modified Draize scale. Score 0 = no erythema/edema; Score 1 = very slight erythema/edema; Score 2 = well-defined erythema/slight edema; Score 3 = moderate to severe erythema/edema; Score 4 = severe erythema/edema. | Immediately after patch removal | 
| Skin Irritation (Erythema) | Erythema was used to determine skin irritation using a modified Draize scale. Score 0 = no erythema; Score 1 = very slight erythema; Score 2 = well-defined erythema; Score 3 = moderate to severe erythema; Score 4 = severe erythema. | 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24) | 
| Skin Irritation (Edema) | Edema was used to determine skin irritation using a modified Draize scale. Score 0 = no edema; Score 1 = very slight edema; Score 2 = slight edema; Score 3 = moderate to severe edema; Score 4 = severe edema. | 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24) | 
| Skin Irritation (Papules and Vesicles) | Papules and vesicles were assessed according to the following scoring criteria: Score 0 = no evidence of papules or vesicles; Score 1 = few papules or vesicles (< 10) observed on the skin site; Score 2 = more papules or vesicles (≥ 10) observed on < 50 % of skin site, diffuse or few clusters; Score 3 = many papules or vesicles observed on ≥ 50% of skin site, diffuse or few clusters; Score 4 = many papules or vesicles observed on > 50% of skin site, with multiple (> 3) clusters. | Immediately after patch removal | 
| Skin Irritation (Papules and Vesicles) | Papules and vesicles were assessed according to the following scoring criteria: Score 0 = no evidence of papules or vesicles; Score 1 = few papules or vesicles (< 10) observed on the skin site; Score 2 = more papules or vesicles (≥ 10) observed on < 50 % of skin site, diffuse or few clusters; Score 3 = many papules or vesicles observed on ≥ 50% of skin site, diffuse or few clusters; Score 4 = many papules or vesicles observed on > 50% of skin site, with multiple (> 3) clusters. | 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24) | 
| Skin Irritation (Other Skin Effects) | Other skin effects were assessed according to the following scoring criteria: Score 0 = no other effects observed; Score 1 = slight glazed appearance; Score 2 = marked glazing; Score 3 = glazing with peeling and cracking; Score 4 = glazing with fissures; Score 5 = film of dried serous exudate covering all or part of the patch site; Score 6 = small petechial erosions and/or scabs. | Immediately after patch removal | 
| Skin Irritation (Other Skin Effects) | Other skin effects were assessed according to the following scoring criteria: Score 0 = no other effects observed; Score 1 = slight glazed appearance; Score 2 = marked glazing; Score 3 = glazing with peeling and cracking; Score 4 = glazing with fissures; Score 5 = film of dried serous exudate covering all or part of the patch site; Score 6 = small petechial erosions and/or scabs. | 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, Tolerability, and Adhesion | See Adverse Event section for Safety assessment. Adhesion was assessed according to the following scoring criteria: Score 0 = approximately > 90% adhered (essentially no lift off the skin); Score 1 = approximately 75% to < 90% adhered (some edges only lifting off the skin); Score 2 = approximately 50% to < 75% adhered (less than half of the system lifting off the skin); Score of 3 = approximately < 50% adhered but not detached (more than half of the system lifting off the skin without falling off); Score of 4 = Patch-system detached (patch /overlay completely off the skin). | Safety was assessed throughout the study. Adhesion was assessed daily and immediately prior to patch removal on Days 8, 15, and 22. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skin Irritation, Donepezil Transdermal Patch System, Elderly, Alzheimer's subjects, Skin Irritation in elderly Alzheimer's subjects