Irritation/Irritant
Conditions
Keywords
Skin Irritation, Donepezil Transdermal Patch System, Elderly, Alzheimer's subjects, Skin Irritation in elderly Alzheimer's subjects
Brief summary
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
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: 1. Upper Back, Upper Arm, Side of Torso (Right) 2. Upper Arm, Side of Torso, Upper Back (Right) 3. Side of Torso, Upper Back, Upper Arm (Right) 4. Upper Back, Side of Torso, Upper Arm (Right) 5. Upper Arm, Upper Back, Side of Torso (Right) 6. Side of Torso, Upper Arm, Upper Back (Right) 7. Upper Back, Upper Arm, Side of Torso (Left) 8. Upper Arm, Side of Torso, Upper Back (Left) 9. Side of Torso, Upper Back, Upper Arm (Left) 10. Upper Back, Side of Torso, Upper Arm (Left) 11. Upper Arm, Upper Back, Side of Torso (Left) 12. 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.
Interventions
DRUG350 mg Donepezil Transdermal Patch
Active and placebo patches will be applied to opposite sides for 7 days.
DRUGPlacebo Patch
Active and placebo patches will be applied to opposite sides for 7 days.
Sponsors
Teikoku Pharma USA, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skin Irritation (Erythema and Edema) | Immediately after patch removal | 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. |
| Skin Irritation (Erythema) | 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24) | 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. |
| Skin Irritation (Edema) | 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24) | 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. |
| Skin Irritation (Papules and Vesicles) | Immediately after patch removal | 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. |
| Skin Irritation (Other Skin Effects) | Immediately after patch removal | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety, Tolerability, and Adhesion | Safety was assessed throughout the study. Adhesion was assessed daily and immediately prior to patch removal on Days 8, 15, and 22. | 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). |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 7 clinical sites during May and June 2009. Patients received 1 placebo patch and 1 Donepezil Transdermal Patch, each applied to opposite sides of the body. The 7-day patches were applied to 1 of 3 consecutive body locations according to 1 of 6 treatment sequences for a total treatment period of 21 days.
Pre-assignment details
Patients diagnosed with Alzheimer's disease who were on a stable course of oral Aricept (10 mg/day) were randomized into the study. Patients discontinued oral Aricept on Day -1 and resumed their original established dose following removal of the last patch.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All patients received the same study treatment, consisting of 1 placebo patch and 1 Donepezil Transdermal Patch, and all patches were applied to the same body locations according to 1 of 6 treatment sequences. The active patch was applied to either the right or the left side of the body according to the randomization schedule. The treatment sequence was repeated for the opposite side of the body for a total of 12 treatment sequences. The 7-day patches were applied to one of 3 body locations (upper arm, upper back, side of torso) for a total treatment period of 21 days. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous All Participants | 79.5 Years STANDARD_DEVIATION 6.47 |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 49 | 14 / 49 | 15 / 49 |
| serious Total, serious adverse events | 1 / 49 | 0 / 49 | 0 / 49 |
Outcome results
Primary
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.
Time frame: 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24)
Population: All patients who received patches are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Upper Back | Skin Irritation (Edema) | 48 hours after patch removal, DTP-system | 0.0 units on a scale | Standard Deviation 0.14 |
| Upper Back | Skin Irritation (Edema) | 24 hours after patch removal, Placebo | 0.1 units on a scale | Standard Deviation 0.41 |
| Upper Back | Skin Irritation (Edema) | 48 hours after patch removal, Placebo | 0.0 units on a scale | Standard Deviation 0.14 |
| Upper Back | Skin Irritation (Edema) | 1 hour after patch removal, Placebo | 0.6 units on a scale | Standard Deviation 0.76 |
| Upper Back | Skin Irritation (Edema) | 24 hours after patch removal, DTP-system | 0.1 units on a scale | Standard Deviation 0.33 |
| Upper Back | Skin Irritation (Edema) | 1 hour after patch removal, DTP-system | 0.6 units on a scale | Standard Deviation 0.73 |
| Upper Arm | Skin Irritation (Edema) | 24 hours after patch removal, DTP-system | 0.1 units on a scale | Standard Deviation 0.34 |
| Upper Arm | Skin Irritation (Edema) | 48 hours after patch removal, Placebo | 0.0 units on a scale | Standard Deviation 0.15 |
| Upper Arm | Skin Irritation (Edema) | 1 hour after patch removal, DTP-system | 0.4 units on a scale | Standard Deviation 0.57 |
| Upper Arm | Skin Irritation (Edema) | 48 hours after patch removal, DTP-system | 0.0 units on a scale | Standard Deviation 0.15 |
| Upper Arm | Skin Irritation (Edema) | 1 hour after patch removal, Placebo | 0.6 units on a scale | Standard Deviation 0.68 |
| Upper Arm | Skin Irritation (Edema) | 24 hours after patch removal, Placebo | 0.2 units on a scale | Standard Deviation 0.38 |
| Side of Torso | Skin Irritation (Edema) | 24 hours after patch removal, Placebo | 0.2 units on a scale | Standard Deviation 0.47 |
| Side of Torso | Skin Irritation (Edema) | 1 hour after patch removal, Placebo | 0.6 units on a scale | Standard Deviation 0.71 |
| Side of Torso | Skin Irritation (Edema) | 1 hour after patch removal, DTP-system | 0.6 units on a scale | Standard Deviation 0.71 |
| Side of Torso | Skin Irritation (Edema) | 48 hours after patch removal, DTP-system | 0.0 units on a scale | Standard Deviation 0.29 |
| Side of Torso | Skin Irritation (Edema) | 24 hours after patch removal, DTP-system | 0.1 units on a scale | Standard Deviation 0.4 |
| Side of Torso | Skin Irritation (Edema) | 48 hours after patch removal, Placebo | 0.1 units on a scale | Standard Deviation 0.25 |
Primary
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.
Time frame: 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24)
Population: All patients who received patches are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Upper Back | Skin Irritation (Erythema) | 24 hours after patch removal, Placebo | 0.6 units on a scale | Standard Deviation 0.8 |
| Upper Back | Skin Irritation (Erythema) | 1 hour after patch removal, DTP-system | 0.9 units on a scale | Standard Deviation 0.73 |
| Upper Back | Skin Irritation (Erythema) | 48 hours after patch removal, Placebo | 0.3 units on a scale | Standard Deviation 0.54 |
| Upper Back | Skin Irritation (Erythema) | 24 hours after patch removal, DTP-system | 0.4 units on a scale | Standard Deviation 0.62 |
| Upper Back | Skin Irritation (Erythema) | 1 hour after patch removal, Placebo | 0.8 units on a scale | Standard Deviation 0.88 |
| Upper Back | Skin Irritation (Erythema) | 48 hours after patch removal, DTP-system | 0.2 units on a scale | Standard Deviation 0.43 |
| Upper Arm | Skin Irritation (Erythema) | 1 hour after patch removal, DTP-system | 0.6 units on a scale | Standard Deviation 0.64 |
| Upper Arm | Skin Irritation (Erythema) | 1 hour after patch removal, Placebo | 0.6 units on a scale | Standard Deviation 0.65 |
| Upper Arm | Skin Irritation (Erythema) | 24 hours after patch removal, Placebo | 0.3 units on a scale | Standard Deviation 0.52 |
| Upper Arm | Skin Irritation (Erythema) | 24 hours after patch removal, DTP-system | 0.4 units on a scale | Standard Deviation 0.57 |
| Upper Arm | Skin Irritation (Erythema) | 48 hours after patch removal, Placebo | 0.2 units on a scale | Standard Deviation 0.46 |
| Upper Arm | Skin Irritation (Erythema) | 48 hours after patch removal, DTP-system | 0.2 units on a scale | Standard Deviation 0.43 |
| Side of Torso | Skin Irritation (Erythema) | 24 hours after patch removal, Placebo | 0.7 units on a scale | Standard Deviation 0.71 |
| Side of Torso | Skin Irritation (Erythema) | 48 hours after patch removal, DTP-system | 0.3 units on a scale | Standard Deviation 0.59 |
| Side of Torso | Skin Irritation (Erythema) | 1 hour after patch removal, Placebo | 0.8 units on a scale | Standard Deviation 0.82 |
| Side of Torso | Skin Irritation (Erythema) | 48 hours after patch removal, Placebo | 0.4 units on a scale | Standard Deviation 0.65 |
| Side of Torso | Skin Irritation (Erythema) | 1 hour after patch removal, DTP-system | 0.7 units on a scale | Standard Deviation 0.74 |
| Side of Torso | Skin Irritation (Erythema) | 24 hours after patch removal, DTP-system | 0.4 units on a scale | Standard Deviation 0.62 |
Primary
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.
Time frame: Immediately after patch removal
Population: All patients who received patches are included in the analysis. Note: The represented data are based on N = 48 for patients who received the placebo patch and the DTP-system on the Upper Back, N = 46 for patients who received the placebo patch on the side of torso, and N = 47 for patients who received the DTP-system on the side of torso.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Upper Back | Skin Irritation (Erythema and Edema) | Edema, DTP-System | 0.6 units on a scale | Standard Deviation 0.76 |
| Upper Back | Skin Irritation (Erythema and Edema) | Erythema, Placebo | 0.9 units on a scale | Standard Deviation 0.85 |
| Upper Back | Skin Irritation (Erythema and Edema) | Erythema, DTP-System | 1.0 units on a scale | Standard Deviation 0.75 |
| Upper Back | Skin Irritation (Erythema and Edema) | Edema, Placebo | 0.6 units on a scale | Standard Deviation 0.82 |
| Upper Arm | Skin Irritation (Erythema and Edema) | Edema, Placebo | 0.6 units on a scale | Standard Deviation 0.68 |
| Upper Arm | Skin Irritation (Erythema and Edema) | Erythema, DTP-System | 0.8 units on a scale | Standard Deviation 0.75 |
| Upper Arm | Skin Irritation (Erythema and Edema) | Edema, DTP-System | 0.5 units on a scale | Standard Deviation 0.68 |
| Upper Arm | Skin Irritation (Erythema and Edema) | Erythema, Placebo | 0.7 units on a scale | Standard Deviation 0.76 |
| Side of Torso | Skin Irritation (Erythema and Edema) | Edema, DTP-System | 0.7 units on a scale | Standard Deviation 0.73 |
| Side of Torso | Skin Irritation (Erythema and Edema) | Erythema, Placebo | 1.1 units on a scale | Standard Deviation 0.89 |
| Side of Torso | Skin Irritation (Erythema and Edema) | Edema, Placebo | 0.7 units on a scale | Standard Deviation 0.71 |
| Side of Torso | Skin Irritation (Erythema and Edema) | Erythema, DTP-System | 1.0 units on a scale | Standard Deviation 0.85 |
Primary
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.
Time frame: Immediately after patch removal
Population: All patients who received patches are included in the analysis. Note: The represented data are based on N = 48 for patients who received the placebo patch and the DTP-system on the Upper Back, N = 46 for patients who received the placebo patch on the side of torso, and N = 47 for patients who received the DTP-system on the side of torso.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Upper Back | Skin Irritation (Other Skin Effects) | DTP-System, Score =6 | 2 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | Placebo, Score ≥1 | 10 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | DTP-System, Score ≥1 | 8 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | Placebo, Score =6 | 2 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | Placebo, Score =6 | 6 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | DTP-System, Score =6 | 4 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | DTP-System, Score ≥1 | 7 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | Placebo, Score ≥1 | 9 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | DTP-System, Score =6 | 2 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | Placebo, Score ≥1 | 8 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | DTP-System, Score ≥1 | 8 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | Placebo, Score =6 | 0 participants |
Primary
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.
Time frame: 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24)
Population: All patients who received patches are included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Upper Back | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, DTP-System, Score =6 | 2 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, DTP-System, Score ≥1 | 9 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, DTP-System, Score =6 | 3 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, DTP-System, Score ≥1 | 2 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, Placebo, Score ≥1 | 10 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, Placebo, Score ≥1 | 3 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, DTP-System, Score =6 | 2 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, Placebo, Score =6 | 2 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, DTP-System, Score ≥1 | 3 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, Placebo, Score ≥1 | 2 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, Placebo, Score =6 | 2 participants |
| Upper Back | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, Placebo, Score =6 | 2 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, Placebo, Score =6 | 6 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, DTP-System, Score =6 | 3 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, Placebo, Score ≥1 | 6 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, DTP-System, Score ≥1 | 7 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, Placebo, Score =6 | 5 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, Placebo, Score =6 | 5 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, DTP-System, Score =6 | 3 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, DTP-System, Score =6 | 4 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, Placebo, Score ≥1 | 7 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, Placebo, Score ≥1 | 9 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, DTP-System, Score ≥1 | 6 participants |
| Upper Arm | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, DTP-System, Score ≥1 | 5 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, DTP-System, Score =6 | 2 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, Placebo, Score =6 | 1 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, Placebo, Score ≥1 | 8 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, DTP-System, Score ≥1 | 8 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, Placebo, Score =6 | 0 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 1 hour after patch removal, DTP-System, Score =6 | 2 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, Placebo, Score ≥1 | 3 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, DTP-System, Score ≥1 | 3 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, Placebo, Score =6 | 1 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, Placebo, Score ≥1 | 1 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 48 hours after patch removal, DTP-System, Score ≥1 | 2 participants |
| Side of Torso | Skin Irritation (Other Skin Effects) | 24 hours after patch removal, DTP-System, Score =6 | 2 participants |
Primary
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.
Time frame: 1, 24, and 48 hours after patch removal (Days 8-10; Days 15-17; Days 22-24)
Population: All patients who received patches are included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Upper Back | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, Placebo, Score >2 | 2 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, Placebo, Score >1 | 9 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, DTP-System, Score >2 | 0 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, Placebo, Score >1 | 5 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, DTP-System, Score >2 | 0 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, DTP-System, Score >1 | 7 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, DTP-System, Score >1 | 5 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, Placebo, Score >2 | 2 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, DTP-System, Score >2 | 1 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, DTP-System, Score >1 | 5 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, Placebo, Score >1 | 5 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, Placebo, Score >2 | 2 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, DTP-System, Score >2 | 0 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, DTP-System, Score >1 | 2 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, DTP-System, Score >1 | 2 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, DTP-System, Score >2 | 0 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, Placebo, Score >1 | 6 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, Placebo, Score >2 | 1 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, Placebo, Score >1 | 2 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, DTP-System, Score >1 | 1 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, Placebo, Score >1 | 4 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, Placebo, Score >2 | 1 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, DTP-System, Score >2 | 0 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, Placebo, Score >2 | 1 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, DTP-System, Score >2 | 0 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, Placebo, Score >2 | 1 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, Placebo, Score >1 | 3 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, DTP-System, Score >1 | 1 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, Placebo, Score >1 | 5 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, DTP-System, Score >1 | 2 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 1 hour after patch removal, DTP-System, Score >2 | 0 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, Placebo, Score >1 | 4 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, DTP-System, Score >1 | 2 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, Placebo, Score >2 | 1 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 24 hours after patch removal, DTP-System, Score >2 | 0 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | 48 hours after patch removal, Placebo, Score >2 | 1 participants |
Primary
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.
Time frame: Immediately after patch removal
Population: All patients who received patches are included in the analysis. Note: The represented data are based on N = 48 for patients who received the placebo patch and the DTP-system on the Upper Back, N = 46 for patients who received the placebo patch on the side of torso, and N = 47 for patients who received the DTP-system on the side of torso.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Upper Back | Skin Irritation (Papules and Vesicles) | Placebo, Score >1 | 9 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | DTP-System, Score >1 | 7 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | Placebo, Score >2 | 2 participants |
| Upper Back | Skin Irritation (Papules and Vesicles) | DTP-System, Score >2 | 1 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | DTP-System, Score >2 | 0 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | Placebo, Score >1 | 5 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | Placebo, Score >2 | 1 participants |
| Upper Arm | Skin Irritation (Papules and Vesicles) | DTP-System, Score >1 | 2 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | DTP-System, Score >2 | 0 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | DTP-System, Score >1 | 2 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | Placebo, Score >2 | 1 participants |
| Side of Torso | Skin Irritation (Papules and Vesicles) | Placebo, Score >1 | 5 participants |
Secondary
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).
Time frame: Safety was assessed throughout the study. Adhesion was assessed daily and immediately prior to patch removal on Days 8, 15, and 22.
Population: Percent of Patients with Adhesion Scores \<2 by Application Day
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Upper Back | Safety, Tolerability, and Adhesion | DTP system - Day 1 | 95.8 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | Placebo - Day 5 | 97.9 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | Placebo - Worst adhesion score over 7 days | 89.6 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | DTP system - Worst adhesion score over 7 days | 83.4 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | Placebo - Day 1 | 97.9 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | Placebo - Day 2 | 100 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | DTP system - Day 2 | 97.8 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | Placebo - Day 3 | 100 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | DTP system - Day 3 | 95.7 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | Placebo - Day 4 | 100 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | DTP system - Day 4 | 95.6 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | DTP system - Day 5 | 93.2 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | Placebo - Day 6 | 93.5 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | DTP system - Day 6 | 95.4 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | Placebo - Day 7 | 91.3 percentage of patients with scores <2 |
| Upper Back | Safety, Tolerability, and Adhesion | DTP system - Day 7 | 93.1 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | Placebo - Day 2 | 100 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | DTP system - Day 2 | 97.8 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | Placebo - Day 3 | 97.9 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | DTP system - Day 6 | 95.4 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | DTP system - Day 3 | 100 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | Placebo - Day 4 | 95.8 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | DTP system - Day 7 | 97.6 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | Placebo - Day 5 | 100 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | Placebo - Day 7 | 97.8 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | DTP system - Day 5 | 100 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | Placebo - Worst adhesion score over 7 days | 93.8 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | DTP system - Worst adhesion score over 7 days | 89.3 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | Placebo - Day 1 | 100 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | DTP system - Day 4 | 97.7 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | DTP system - Day 1 | 97.9 percentage of patients with scores <2 |
| Upper Arm | Safety, Tolerability, and Adhesion | Placebo - Day 6 | 97.8 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | Placebo - Day 5 | 100 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | Placebo - Day 2 | 100 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | Placebo - Day 6 | 97.9 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | DTP system - Day 4 | 97.8 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | DTP system - Day 2 | 97.9 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | DTP system - Day 7 | 93.0 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | DTP system - Worst adhesion score over 7 days | 85.4 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | Placebo - Day 3 | 100 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | Placebo - Day 7 | 95.8 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | DTP system - Day 1 | 100 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | DTP system - Day 3 | 95.8 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | DTP system - Day 6 | 95.5 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | Placebo - Worst adhesion score over 7 days | 93.8 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | Placebo - Day 4 | 100 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | DTP system - Day 5 | 93.3 percentage of patients with scores <2 |
| Side of Torso | Safety, Tolerability, and Adhesion | Placebo - Day 1 | 100 percentage of patients with scores <2 |