BAY1003803 Single and Multiple Dose Escalation, Safety, Tolerability and Pharmacokinetics Study

Study Overview
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Brief Summary
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Systemic safety following single and multiple dermal administration of BAY1003803

Official Title
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Escalating Dose Study for Safety, Tolerability and Pharmacokinetics After Single and Multiple Dermal Administration of Two BAY1003803 Formulation Types With Two Concentrations Each in Healthy Male Volunteers, Applying a Double-blind, Vehicle-controlled Design and Including a Positive Control Group

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: BAY1003803 0.01% lipophilic cream
* Drug: BAY1003803 0.1% lipophilic cream
* Drug: BAY1003803 0.01% ointment
* Drug: BAY1003803 0.1% ointment
* Drug: Lipophilic cream vehicle
* Drug: Ointment vehicle
* Drug: Clobetasol propionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subject Age: 18 to 64 years (inclusive) at the first screening visit Body mass index (BMI): above or equal 18 and below or equal 30 kg / m² at the first screening visit Non-smoker at least 3 months prior to study start and during the study Healthy skin on which reddening can be easily recognized Exclusion Criteria: A history of relevant diseases, especially incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, excretion and effect of the study drugs will not be normal, dermal diseases, diseases which present a risk for subjects to be treated with glucocorticoid receptor agonists (e.g. gastric ulcers, cornea ulcer, colitis ulcerosa, severe infections, glaucoma, diabetes, myocardial infarction, thromboembolic disease, hypertension, thyroid disease, tuberculosis, myasthenia gravis, osteoporosis, psychiatric diseases) Infections and febrile illness within 4 week before the first study drug administration Use of systemic or topical medicines or substances which oppose the study objectives or which might influence them Inoculations with live vaccine within 8 weeks before the first study drug administration Signs of irritation or folliculitis or any other dermatological conditions in the test areas that would interfere with the planned assessments as judged by the Investigators Human leukocyte antigen-DR (HLA-DR) < 15000 AB/monocyte

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY1003803<br>Topical treatment: dose escalating in 9 steps from 0.13 mg to 61.7 mg per subject | Drug: BAY1003803 0.01% lipophilic cream<br>* Topical administration for 22 h per day<br>Drug: BAY1003803 0.1% lipophilic cream<br>* Topical administration for 22 h per day<br>Drug: BAY1003803 0.01% ointment<br>* Topical administration for 22 h per day<br>Drug: BAY1003803 0.1% ointment<br>* Topical administration for 22 h per day<br>|
| Placebo Comparator: Placebo<br>Topical treatment using matching amount of placebo | Drug: Lipophilic cream vehicle<br>* Topical administration for 22 h per day<br>Drug: Ointment vehicle<br>* Topical administration for 22 h per day<br>|
| Active Comparator: Clobetasol propionate<br>Topical treatment using 16.5 mg of clobetasol propionate per subject | Drug: Clobetasol propionate<br>* Topical administration for 22 h per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol serum levels for safety |  | Up to 2 weeks | 
| Frequency of treatment-emergent adverse events (TEAEs) |  | Up to 2 weeks | 
| Nature of treatment-emergent adverse events (TEAEs) |  | Up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monocytic human leukocyte antigen-DR (HLA-DR) expression (Part 1, single dose) |  | Day 1 to 3 at 8:00 am | 
| Monocytic human leukocyte antigen-DR (HLA-DR) expression (Part 2, multiple dose) |  | Day 1 to 8 at 8:00 am | 
| Maximum plasma concentration (Cmax) after single dose of BAY1003803 |  | At pre-dose, 1.5, 3, 5, 7, 9, 11, 13, 15, 21, 22, 23, 24 hours | 
| Area under the plasma concentration vs. time curve from zero to infinity (AUC) after single dose of BAY1003803 |  | At pre-dose, 1.5, 3, 5, 7, 9, 11, 13, 15, 21, 22, 23, 24, 27, 31, 35, 39, 47 hours | 
| Area under the curve from time zero to 22 hours [AUC(0-22)] after single dose of BAY1003803 |  | At pre-dose, 1.5, 3, 5, 7, 9, 11, 13, 15, 21, 22 hours | 
| Maximum plasma concentration (Cmax,md) after multiple dose of BAY1003803 |  | At pre-dose, 3, 7, 9, 11, 13, 22, 23 hours (Day 1); At pre-dose, 3, 7, 9, 11, 13, 22, 23, 24 hours (Day 2 and Day 6) | 
| Area under the curve from time zero to 24 hours [AUC(0-24)md] after multiple dose of BAY1003803 |  | At pre-dose, 3, 7, 9, 11, 13, 22, 23 hours (Day 1); At pre-dose, 3, 7, 9, 11, 13, 22, 23, 24 hours (Day 2 and Day 6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Healthy volunteers