Intervention: Ovatodiolide
Trial phase: Phase 1 | Phase 2
SMILES: C=C1C(=O)OC2C=C(C)CC3C=C(CCC=C(C)CCC12)C(=O)O3
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 3
Group description: Subjects topically apply AR100DP1 twice per day with at least 4 hour interval. The daily dosage of 2.5% AR100DP1 topical administration is 62.5 mg/day (2.5% × 1,250 × 2 = 62.5).
Eligibility criteria:
Inclusion Criteria:

Phase I:

Dated and signed informed consent
Either gender, ≥ 20 years old (the legal age of consent majority is 20 years old in Taiwan)
Healthy subjects, who have no clinically relevant abnormalities, identified by medical history, physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory tests
Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures
Healthy skin on which reddening can be easily recognized in the area of the test fields, evaluated by the investigator
Subject of childbearing potential must agree to use abstinence to intercourse, or highly effective contraceptives from signing informed consent to 14 days after the last dose of study drug administration

At least two forms of effective birth control must be adopted for contraception, and one of which must be a barrier method. Acceptable forms include:

Established use of oral, injected or implanted hormonal methods of contraception
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Barrier methods of contraception: condom (highly recommended with spermicide), or occlusive cap (diaphragm or cervical/vault caps)

Phase IIa:

Dated and signed informed consent
Either gender, ≥ 20 years old (the legal age of consent majority is 20 years old in Taiwan)
Confirmed clinical diagnosis of atopic dermatitis (based on the criteria of Hanifin and Rajka for AD)
With at least 0.5% body surface area (BSA) as target lesion area(s)
Clinical diagnosis of AD that has been clinically stable, which means the IGA score stays as 2 or 3 when evaluated for ≥ 4 weeks at the investigator's discretion prior to Screening Visit
With Investigator's Global Assessment (IGA) score of 2 (mild) or 3 (moderate) at screening
Subject of childbearing potential must agree to use abstinence to intercourse, or highly effective contraceptives from signing informed consent to 14 days after the last dose of study drug administration

At least two forms of effective birth control must be adopted for contraception, and one of which must be a barrier method. Acceptable forms include:

Established use of oral, injected or implanted hormonal methods of contraception
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Barrier methods of contraception: condom (highly recommended with spermicide), or occlusive cap (diaphragm or cervical/vault caps)

Exclusion Criteria:

Phase I:

Subjects who have any visible skin disease at the application site which, in the opinion of the investigator, will interfere with the evaluation of the test site reaction
Subjects who have a history of AD, psoriasis and/or active AD/eczema
Subjects who have damaged skin in or around the test sites, including sunburn, excessively deep tans, uneven skin tones, tattoos, scars, excessive hair, numerous freckles, or other disfigurations of the test site
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing)

Phase IIa:

Unstable or actively infected AD judged by the investigator.
Active or potentially recurrent dermatologic condition other than atopic dermatitis that may confound evaluation (e.g. fungal infection), judged by the investigator.
Received systemic medication including corticosteroid, immunosuppressant, anti-histamine, phototherapy, or other therapy, which could affect AD within 4 weeks before Screening. However, subjects are allowed to enter the study if subjects have been taking at least 2 weeks of fixed dose anti-histamine prior to Screening and this application does not affect the study judged by the investigator

Received topical medication including corticosteroid, immunosuppressant, anti-histamine, phototherapy, calcineurin inhibitors, or other therapy for AD on the target lesion area(s) within 1 week before Screening

The following exclusion criteria are applied for all subjects in Phase I/IIa study:

Plan to receive immunosuppressive agents (including azathioprine, mycophenolate, cyclophosphamide, chlorambucil, methotrexate, cyclosporine), or systemic steroid with equivalent dosage higher than prednisolone 30 mg/day for more than 14 days at Screening
Unwilling or unable to comply with the criteria in Life Style Guidelines during the study
History of use of biologic therapy (including intravenous immunoglobulin) within 12 weeks or 5 half-lives (whichever is longer) prior to Screening
Received any other investigational drug within 4 weeks prior to Screening
Required or received systemic CYP3A4 inhibitors with strong potency within 1 week prior to screening, including but not limited to clarithromycin, itraconazole, nefazodone and atazanavir, evaluated by the investigator
Treatment for any type of cancer (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin, curatively treated with cryosurgery or surgical excision only) within 5 years before screening
Had surgery within 4 weeks prior to Screening Visit, or plan to have surgery during the study
Allergies requiring acute or chronic treatment at the investigator's discretion
Known hypersensitivity to any of the components of the study drug
Active clinically serious infection or history of human immunodeficiency virus (HIV) infection

Any of the following serum test abnormalities:

Total bilirubin > 1.5 × ULN
AST or ALT > 3.0 × ULN
Serum albumin < 2.5 g/dL
Creatinine > 1.5 × ULN
Any other ≥ Grade 2 (grading of vaccine clinical trials for Phase I and NCI-CTCAE v5.0 for Phase IIa) laboratory abnormality at baseline (other than those listed above)
With ongoing acute diseases or within the past 2 years serious medical conditions (e.g. concomitant illness) such as cardiovascular (e.g. New York Heart Association (NYHA) grade III or IV), hepatic (e.g. Child-Pugh Class C), psychiatric condition (e.g. alcoholism, drug abuse), medical history, physical findings, or laboratory abnormality that in the investigators' opinion could interfere with the results of the trial or adversely affect the safety of the subject
Female subject who is lactating or has positive urine pregnancy test at screening
Other conditions not suitable for participating in this study judged by the investigator