A Trial to Explore Symptomatic Therapy for Application Site Reaction to SPM962 in Healthy Subject

Study Overview
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Brief Summary
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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

Official Title
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An Open-Label Trial to Explore Symptomatic Therapy for Application Site Reaction to SPM962 in Healthy Subject

Conditions
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Healthy

Intervention / Treatment
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* Drug: Topical steroid (Dexamethasone)
* Drug: Topical antihistamine (Diphenhydramine)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical Steroid<br>Topical medication of steroid (Dexamethasone) to the application sites after the patch removal | Drug: Topical steroid (Dexamethasone)<br>* 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<br>|
| Experimental: Topical antihistamine<br>Topical medication of antihistamine(Diphenhydramine) to the application sites after the patch removal | Drug: Topical antihistamine (Diphenhydramine)<br>* 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<br>|
| No Intervention: No-treatment<br>No treatment to the application sites after the patch removal | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 hours after 2 mg/24 hr patch removal | 
| 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). | 24 hours after 2 mg/24 hr patch removal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 72 hours after patch removal | 
| 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). | Up to 96 hours after patch removal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SPM 962, rotigotine, application site reaction