Healthy
Conditions
Keywords
SPM 962, rotigotine, application site reaction
Brief summary
To investigate the efficacy of symptomatic therapy with topical steroids and antihistamines for application site reaction (ASR) after administration of SPM 962 in healthy subjects
Interventions
DRUGTopical steroid (Dexamethasone)
for SPM 962: 1 mg/24h patch for 48 hours as Acceleration period, then 2 mg/24h patch to the other site for 24 hours as Dose-escalation period, for steroid: twice daily administration of Dexamethasone (1 mg/g cream) to the application sites after the patch removal
DRUGTopical antihistamine (Diphenhydramine)
for SPM 962: 1 mg/24h patch for 48 hours as Acceleration period, then 2 mg/24h patch to the other site for 24 hours as Dose-escalation period, for antihistamine: twice daily administration of Diphenhydramine (10 mg/g cream) to the application sites after the patch removal
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is a male or female and aged between 20 and 45 years of age (inclusive) * Subject is of normal body weight as determined by a body-mass index (BMI) between 18 and 28 kg/m2 * Subject is healthy as determined by EA (medical history, physical examination, skin evaluation, vital signs, ECG, hematology, clinical chemistry, urinalysis) * Subject is surgically sterile; subject has been postmenopausal for at least 12 consecutive months if female; or subject agrees to remain abstinent or to follow two acceptable methods of birth control from EA to the end of observation period. (fore male and female subjects)
Exclusion criteria
* Subject has a history or complication of epilepsy and/or seizures * Subject has clinically relevant changes in the ECG, such as second- or third-degree AV block, a complete bundle branch block, prolongation of the QRS complex over 120 ms, or of the QTcB (QT interval corrected for HR by Bazett´s formula) over 500 ms at EA * Subject has a clinically relevant hepatic dysfunction * Subject has a clinically relevant renal dysfunction * Subject has a history of significant skin hypersensitivity to adhesives or other transdermal products or recent unresolved contact dermatitis * Subject has a history or complication of atopic or eczematous dermatitis, psoriasis, and/or an active skin disease or skin tumors * Subject has more than 1 known or suspected drug hypersensitivity, in particular to any component of the trial medication * Subject has a history of chronic alcohol or drug abuse within the last 5 years * Subject is tested positive for HIV-1/2Ab, HBsAg or HCV-Ab * Subject tests positive for alcohol and/or drugs at EA * Subject is taking any prohibited concomitant medication * Subject has a history or complication of narrow angle glaucoma * Subject has a history or complication of respiratory or cardiovascular disorders (e.g., heart failure, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia, or myocardial infarction) * Subject has a history or complication of psychic abnormality, psychiatric or neurologic illness, or autonomic neuropathy * Subject has a history or complication of diabetes mellitus and/or thyroid dysfunction, especially hyperthyroidism or other endocrine disorders * Subject has a history or complication of malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skin Irritation Score of the Application Site | 24 hours after 2 mg/24 hr patch removal | Skin irritation score of the application site 24 hours after 2 mg/24 hour patch removal (dose-escalation period) and difference between Steroid or Antihistamine and No-treatment. The scale scoring criteria are 0(-): Negative, 0.5(±): Faint erythema, 1(+): Erythema, 2(++): Erythema + edema, 3(+++): Erythema + edema + papules, serous papule, vesicles, 4(++++): Coalescing vesicles. |
| Itching of Application Site Evaluated by the Visual Analogue Scale (VAS) | 24 hours after 2 mg/24 hr patch removal | Itching of application site evaluated by the visual analogue scale (VAS) 24 hours after 2 mg/24 hour patch removal (dose-escalation period) and difference between Steroid or Antihistamine and No-treatment. The score ranges from 0 (no itching) to 100 (strongest imaginable itching). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Skin Irritation Score After Patch Removal | Up to 72 hours after patch removal | Numbers of subjects with each skin irritation score. The scale scoring criteria are 0(-): Negative, 0.5(±): Faint erythema, 1(+): Erythema, 2(++): Erythema + edema, 3(+++): Erythema + edema + papules, serous papule, vesicles, 4(++++): Coalescing vesicles. |
| Itching of Application Site Evaluated by VAS After Patch Removal | Up to 96 hours after patch removal | Changes of itching of application site evaluated by VAS after patch removal (acceleration and dose-escalation periods). The score ranges from 0 (no itching) to 100 (strongest imaginable itching). |
Countries
South Korea
Participant flow
Pre-assignment details
A total of 120 eligible subjects received the IMP treatment at least once, and 3 of them were withdrawn from the trial before topical treatment allocation due to subject request (1 subject) and for lack of efficacy evaluation (2 subjects).
Participants by arm
| Arm | Count |
|---|---|
| Topical Steroid Topical medication of steroid (Dexamethasone) to the application sites after the patch removal | 38 |
| Topical Antihistamine Topical medication of antihistamine(Diphenhydramine) to the application sites after the patch removal | 40 |
| No-treatment No treatment to the application sites after the patch removal | 39 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Topical Steroid | Topical Antihistamine | No-treatment | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 40 Participants | 39 Participants | 117 Participants |
| Age, Continuous | 26.7 years STANDARD_DEVIATION 4.2 | 26.7 years STANDARD_DEVIATION 4.8 | 26.1 years STANDARD_DEVIATION 3.7 | 26.5 years STANDARD_DEVIATION 4.3 |
| Region of Enrollment Korea, Republic of | 38 participants | 40 participants | 39 participants | 117 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 38 Participants | 40 Participants | 39 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 41 / 120 |
| serious Total, serious adverse events | 0 / 120 |
Outcome results
Primary
Itching of Application Site Evaluated by the Visual Analogue Scale (VAS)
Itching of application site evaluated by the visual analogue scale (VAS) 24 hours after 2 mg/24 hour patch removal (dose-escalation period) and difference between Steroid or Antihistamine and No-treatment. The score ranges from 0 (no itching) to 100 (strongest imaginable itching).
Time frame: 24 hours after 2 mg/24 hr patch removal
Population: FAS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Topical Steroid | Itching of Application Site Evaluated by the Visual Analogue Scale (VAS) | 1.6 Scores on a scale |
| Topical Antihistamine | Itching of Application Site Evaluated by the Visual Analogue Scale (VAS) | 0.4 Scores on a scale |
| No-treatment | Itching of Application Site Evaluated by the Visual Analogue Scale (VAS) | 0.9 Scores on a scale |
Primary
Skin Irritation Score of the Application Site
Skin irritation score of the application site 24 hours after 2 mg/24 hour patch removal (dose-escalation period) and difference between Steroid or Antihistamine and No-treatment. The scale scoring criteria are 0(-): Negative, 0.5(±): Faint erythema, 1(+): Erythema, 2(++): Erythema + edema, 3(+++): Erythema + edema + papules, serous papule, vesicles, 4(++++): Coalescing vesicles.
Time frame: 24 hours after 2 mg/24 hr patch removal
Population: Full analysis set (FAS) subjects with a score of ≥ 0.5 (±) at Day 3
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Topical Steroid | Skin Irritation Score of the Application Site | 0.237 Scores on a scale |
| Topical Antihistamine | Skin Irritation Score of the Application Site | 0.289 Scores on a scale |
| No-treatment | Skin Irritation Score of the Application Site | 0.250 Scores on a scale |
Secondary
Itching of Application Site Evaluated by VAS After Patch Removal
Changes of itching of application site evaluated by VAS after patch removal (acceleration and dose-escalation periods). The score ranges from 0 (no itching) to 100 (strongest imaginable itching).
Time frame: Up to 96 hours after patch removal
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topical Steroid | Itching of Application Site Evaluated by VAS After Patch Removal | 3 hours after patch removal | -2.8 Scores on a scale | Standard Deviation 6.9 |
| Topical Steroid | Itching of Application Site Evaluated by VAS After Patch Removal | 6 hours after patch removal | -3.3 Scores on a scale | Standard Deviation 7.9 |
| Topical Steroid | Itching of Application Site Evaluated by VAS After Patch Removal | 24 hours after patch removal | -3.9 Scores on a scale | Standard Deviation 10 |
| Topical Steroid | Itching of Application Site Evaluated by VAS After Patch Removal | 48 hours after patch removal | -3.9 Scores on a scale | Standard Deviation 10.5 |
| Topical Steroid | Itching of Application Site Evaluated by VAS After Patch Removal | 72 hours after patch removal | -4.1 Scores on a scale | Standard Deviation 10 |
| Topical Steroid | Itching of Application Site Evaluated by VAS After Patch Removal | 96 hours after patch removal | -4.3 Scores on a scale | Standard Deviation 10.1 |
| Topical Antihistamine | Itching of Application Site Evaluated by VAS After Patch Removal | 96 hours after patch removal | -3.8 Scores on a scale | Standard Deviation 8.9 |
| Topical Antihistamine | Itching of Application Site Evaluated by VAS After Patch Removal | 3 hours after patch removal | -3.0 Scores on a scale | Standard Deviation 9 |
| Topical Antihistamine | Itching of Application Site Evaluated by VAS After Patch Removal | 48 hours after patch removal | -3.6 Scores on a scale | Standard Deviation 9 |
| Topical Antihistamine | Itching of Application Site Evaluated by VAS After Patch Removal | 72 hours after patch removal | -3.8 Scores on a scale | Standard Deviation 8.9 |
| Topical Antihistamine | Itching of Application Site Evaluated by VAS After Patch Removal | 6 hours after patch removal | -3.3 Scores on a scale | Standard Deviation 8.6 |
| Topical Antihistamine | Itching of Application Site Evaluated by VAS After Patch Removal | 24 hours after patch removal | -2.6 Scores on a scale | Standard Deviation 7 |
| No-treatment | Itching of Application Site Evaluated by VAS After Patch Removal | 6 hours after patch removal | -2.3 Scores on a scale | Standard Deviation 5 |
| No-treatment | Itching of Application Site Evaluated by VAS After Patch Removal | 24 hours after patch removal | -2.6 Scores on a scale | Standard Deviation 4.7 |
| No-treatment | Itching of Application Site Evaluated by VAS After Patch Removal | 96 hours after patch removal | -3.0 Scores on a scale | Standard Deviation 5.1 |
| No-treatment | Itching of Application Site Evaluated by VAS After Patch Removal | 48 hours after patch removal | -2.9 Scores on a scale | Standard Deviation 5.1 |
| No-treatment | Itching of Application Site Evaluated by VAS After Patch Removal | 3 hours after patch removal | -2.2 Scores on a scale | Standard Deviation 4.6 |
| No-treatment | Itching of Application Site Evaluated by VAS After Patch Removal | 72 hours after patch removal | -3.0 Scores on a scale | Standard Deviation 5.1 |
Secondary
Skin Irritation Score After Patch Removal
Numbers of subjects with each skin irritation score. The scale scoring criteria are 0(-): Negative, 0.5(±): Faint erythema, 1(+): Erythema, 2(++): Erythema + edema, 3(+++): Erythema + edema + papules, serous papule, vesicles, 4(++++): Coalescing vesicles.
Time frame: Up to 72 hours after patch removal
Population: FAS subjects with a score of ≥ 0.5 (±) at Day 3
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topical Steroid | Skin Irritation Score After Patch Removal | - (72 hours after patch removal) | 94.4 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | ± (1 hour after patch removal) | 63.2 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | ± (24 hours after patch removal) | 36.8 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | ± (72 hours after patch removal) | 5.6 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | ± (48 hours after patch removal) | 10.5 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | + (24 hours after patch removal) | 5.3 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | - (24 hours after patch removal) | 57.9 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | - (1 hour after patch removal) | 5.3 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | - (48 hours after patch removal) | 89.5 Percentage of participants |
| Topical Steroid | Skin Irritation Score After Patch Removal | + (1 hour after patch removal) | 31.6 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | - (48 hours after patch removal) | 94.7 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | ± (48 hours after patch removal) | 5.3 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | + (1 hour after patch removal) | 38.9 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | - (72 hours after patch removal) | 94.7 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | - (1 hour after patch removal) | 5.6 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | ± (72 hours after patch removal) | 5.3 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | - (24 hours after patch removal) | 52.6 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | ± (24 hours after patch removal) | 36.8 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | ± (1 hour after patch removal) | 55.6 Percentage of participants |
| Topical Antihistamine | Skin Irritation Score After Patch Removal | + (24 hours after patch removal) | 10.5 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | ± (72 hours after patch removal) | 10.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | ± (1 hour after patch removal) | 45.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | + (1 hour after patch removal) | 45.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | - (24 hours after patch removal) | 60.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | ± (24 hours after patch removal) | 30.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | + (24 hours after patch removal) | 10.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | - (48 hours after patch removal) | 80.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | ± (48 hours after patch removal) | 20.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | - (72 hours after patch removal) | 90.0 Percentage of participants |
| No-treatment | Skin Irritation Score After Patch Removal | - (1 hour after patch removal) | 10.0 Percentage of participants |