Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis
Brief summary
The purpose of this study is to evaluate the safety and efficacy of 2 doses of S-777469 in patients with atopic dermatitis.
Interventions
DRUGS-777469 400 mg
S-777469 400 mg BID
DRUGS-777469 800 mg
S-777469 800 mg BID
DRUGPlacebo
Placebo BID
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Screening Inclusion Criteria: Each patient must meet all of the following inclusion criteria to be screened and enrolled into the single-blind period: * Males or females between 18 and 65 years of age at the time of obtaining the written informed consent * Patient understands the study procedures and agrees to participate in the study by giving written informed consent * Patient agrees to allow digital photographs of atopic dermatitis (AD)-affected target areas during the study * Patient satisfies the diagnostic criteria for AD as defined by the criteria of Hanifin and Rajka (Acta Derm Venereol.1980;92\[suppl\]:44-47; J Am Acad Dermatol.2003;49\[6\]:1088-1095), as follows: Must have 3 or more basic features: * Pruritis * Typical morphology and distribution: flexural lichenification or linearity * Chronic or chronically relapsing dermatitis * Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis) Plus 3 or more minor features: * Xerosis * Ichthyosis/palmar hyperlinearity/keratosis pilaris * Early age of onset * Tendency toward cutaneous infections (esp. Staphylococcus aureus and Herpes simplex) /impaired cell-mediated immunity * Tendency toward non-specific hand or foot dermatitis * Nipple eczema * Cheilitis * Recurrent conjunctivitis * Dennie-Morgan infraorbital fold * Keratoconus * Anterior subcapsular cataracts * Orbital darkening * Facial pallor/facial erythema * Pityriasis alba * Anterior neck folds * Itch when sweating * Intolerance to wool and lipid solvents * Perifollicular accentuation * Food intolerance * Course influenced by environmental/emotional factors * White dermographism/delayed blanch * Immediate (type I) skin test reactivity (Provide test results within one year of Screening date.) * Elevated serum IgE. * Patient has negative laboratory results for hepatitis B surface antigen and IgG anti- Hepatitis B core, hepatitis C virus antibodies, and human immunodeficiency virus (HIV) antibody tests at screening * Serum creatinine and blood urea nitrogen are in the normal range at screening * Female patients of child bearing potential must have a negative pregnancy test at screening and Day-14 * Patient has a negative screen for drugs of abuse at screening * Patient does not have a history or clinical manifestations of significant metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal or urological disease * Patient does not have liver function test results \>1.25 the upper limit of normal NOTE: Under no circumstances should a patient who did not qualify regarding liver function tests (alanine aminotransferase \[ALT\] and/or aspartate aminotransferase \[AST\]) be re-screened and/or re-qualified * Patient does not have QTc \> 450 (males) or \> 470 (females) at screening Randomization Inclusion Criteria: Patients eligible to be randomized to double-blind treatment must satisfy all of the following inclusion criteria: * Patient has all of the following at the end of the single-blind period (Day 1, just before randomization to study drug): * Physician's Global Assessment (PGA) ≥ 2 but ≤ 4. * The average of the scores recorded from the evening of Day -3 to the morning of Day 1 (Baseline value) of the Numerical Rating Scale (NRS) is ≥ 4. * The average of the scores recorded from the evening of Day -3 to the morning of Day 1 (Baseline value) of the Behavior Rating Scale (BRS) is ≥ 2 * Patient has negative laboratory results for hepatitis B surface antigen, IgE anti-Hepatitis B core, hepatitis C virus antibodies, and HIV antibody tests at screening * Female patients of child bearing potential must have a negative pregnancy test at screening, single-blind period (Day-14) and baseline (Day 1) * Serum creatinine and blood urea nitrogen are in the normal range at screening * Patient has negative screen for drugs of abuse at screening and single-blind (Day-14) * Use of adequate birth control by men and women, if of reproductive potential and sexually active. Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception throughout the duration of the study and for 2 weeks after the last dose of study drug * For females, adequate birth control methods will be defined as: hormonal contraceptives, intrauterine device or double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam * For males adequate birth control methods will be defined as double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam * For females, menopause is defined as one year without menses; if in question, a follicle-stimulating hormone of \>40 U/ml must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable * Patient has not used any treatments for AD prior to Day 1, using the following time periods: * Systemic (inhaled, oral, suppository or immediate release injectable, depot or sustained-release injectable) corticosteroids, cytostatic drugs, or other immunosuppressant drugs: 5 weeks prior to Day 1 * Topical immunosuppressant drugs: 4 weeks prior to Day 1 * Phototherapy, specific desensitization therapy, nonspecific disease-modulating therapy and elimination diet therapy: 4 weeks prior to Day 1 * Any drugs that are known inhibitors or inducers of Cytochrome P450 isozyme cytochrome CYP2C9: 2 weeks prior to Day 1 * Systemic antibiotics: 4 weeks prior to Day 1 * Topical steroids or tar preparations: 2 weeks prior to Day 1 * Antihistamines, histamine-added γ-globulin preparations, desensitization therapy, or other nonspecific disease-modifying therapies: 2 weeks prior to Day 1 * Herbal preparation, cosmetic or emollient preparations other than those issued during the screening and single-blind periods: 2 weeks prior to Day 1. Use of cosmetic make-up will be allowed * Acetaminophen, acetaminophen-containing products, or non-steroidal anti-inflammatories: 2 weeks prior to Day 1 * Any other investigational drug or device within 8 weeks prior to Day 1 * Patient is willing to completely avoid the use of any prescription or nonprescription treatments for AD , including over-the-counter drugs or any topical preparations, other than those topical emollient preparations provided by the study site during the screening period and thereafter, as needed. Use of hormone replacement therapy (for postmenopausal females) and/or use of hormonal contraceptive(s), intrauterine device, or double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam will be allowed. Use of topical antibiotics will be allowed during the study
Exclusion criteria
Patients satisfying any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of S-777469 was assessed by Physician's Global Assessment (PGA) and Numerical Rating Scale (NRS) | Change from baseline to 12 weeks | Physician's Global Assessment |
| Safety was assessed by repeated clinical evaluation and evaluation of treatment-emergent adverse events. It included vital signs, medical history, concomitant medications, physical examination, 12-lead ECGs, and standard clinical laboratory safety tests | Baseline to 12 weeks | Safety, determined by Adverse event frequency and changes in laboratory values |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy was assessed by PGA, NRS, Behavioral Rating Scale, Eczema Area and Severity Index Score, Investigator panel treatment-blind comparative review ratings of digital photography of affected areas, and Thymus and Activation-Regulated Chemokine | Changes from baseline to various pre-defined time-points during the 12 week study | Assessment of PGA, NRS, Behavioral Rating Scale, Eczema Area and Severity Index Score, Investigator panel treatment-blind comparative review ratings of digital photography of affected areas, and Thymus and Activation-Regulated Chemokine |
| Pharmacokinetic analysis of the concentration of unchanged parent drug (S-777469) in trough samples | From Baseline during Week 1 | The concentration of S-777469 will be evaluated to determine when steady state is achieved |
Countries
United States
Outcome results
None listed