A Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 2 Doses of S-777469 in Patients With Atopic Dermatitis

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 exclusion criteria are not eligible for enrollment
into the double-blind treatment period:

- Patient is under the age of legal consent, is mentally or legally incapacitated and/or
has significant emotional problems at the time of study entry

- Patient has an active dermatologic condition other than AD which may confound the
diagnosis or evaluation of AD, such as scabies, allergic contact dermatitis,
seborrheic dermatitis, cutaneous lymphoma, or psoriasis

- Patient has a history of malignancy not in remission for >5 years, with the exception
of cutaneous basal cell carcinoma and cutaneous squamous cell carcinoma

- Presence of comorbid conditions that would preclude participation in the study,
including:

- Immune compromised state, including recent chemotherapy, immunotherapy, or organ
transplant

- History or clinical manifestations of significant metabolic, hepatic, renal,
hematological, pulmonary, cardiovascular, gastrointestinal or urological disease

- Signs and symptoms of eczema herpeticum within the preceding 12 months or
cellulitis within preceding 3 months

- Positive results for HIV infection at screening

- History or clinical manifestations of significant neurological (e.g., epilepsy)
or psychiatric disorders (e.g., history of suicide attempt; history of
psychiatric episodes resulting in hospitalization)

- An active intercurrent infection

- History of clinically significant hypersensitivity, anaphylaxis, or allergies to
any drug compound, which resulted in a severe adverse event

- Liver function tests (ALT, AST) >1.25 times the upper limit of normal at
Screening. (refer to Covance Lab Manual for reference ranges) Note: Under no
circumstances should a patient who did not qualify regarding liver function tests
(ALT and/or AST) be re-screened and/or re-qualified

- Patient has any acute or chronic condition or prior therapy that, in the opinion of
the Investigator, would limit the patient's ability to complete and/or participate in
this clinical study or otherwise would make the patient unsuitable for this study

- Patient has a history of drug abuse within 1 year prior to Day 1

- Patient consumes excess amounts of alcohol, defined as exceeding an average of 14
drinks/week (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard
liquor, or any combination of them) within 2 months prior to Day -14 (beginning of
single-blind period) or is unwilling to comply with the restricted use of alcohol (as
defined above, no more than 14 drinks/week) from screening, throughout the study, and
until study completion (follow-up visit).

- Patient uses any prohibited concomitant medications at any time during the study

- Patient is pregnant or lactating or intends to become pregnant or, in the case of a
male patient, intends to father a child during the study period and for 2 weeks after
the last dose of study medication

- Patient has poor peripheral venous access that may limit blood sampling for clinical
laboratory or pharmacokinetic analysis

- Patient has participated in any other investigational study drug or device trial in
which receipt of an investigational study drug or device occurred within 8 weeks prior
to Day 1

- Prior exposure to S-777469

- Any reason which, in the opinion of the Investigator, interferes with the ability of
the patient to participate in or complete the trial