The purpose of this study is to evaluate the interstitial concentrations using the open-flow microperfusion device and plasma pharmacokinetics following multiple doses of povorcitinib or topical ruxolitinib cream in healthy adult participants.

Inclusion Criteria:

• Ability to comprehend and willingness to sign a written ICF for the study.
• Aged 18 to 65 years, inclusive, at the time of signing the ICF.
• Body mass index between 18.0 and 30.5 kg/m2, inclusive.
• No clinically significant findings on screening evaluations (clinical, laboratory, and ECG).
• Ability to swallow and retain oral medication.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• History of uncontrolled or unstable cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening.
• Participants with any history of an autoimmune disease diagnosis.
• History of cardiovascular, cerebrovascular, peripheral vascular, or thrombotic disease or uncontrolled hypertension.
• History or presence of an abnormal ECG.
• Presence or history of a malabsorption syndrome possibly affecting drug absorption (eg, Crohn's disease or chronic pancreatitis).
• Any malignancies or history of malignancies with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ.
• Current or recent (within 3 months of screening) clinically significant gastrointestinal disease or surgery (including cholecystectomy; excluding appendectomy and hernia repair) that could affect the absorption of study drug.
• Any major surgery within 4 weeks of screening.
• Donation of blood to a blood bank or participation in a clinical study (except a screening visit) within 4 weeks of screening (within 2 weeks for plasma-only donation).
• Blood transfusion within 4 months of check-in (Day -1).
• Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment (includes latent treated tuberculosis).
• Known tuberculosis infection that is active or participant-reported history of tuberculosis or treatment thereof.
• Positive test for HBV, HCV, or HIV. Participants whose results are compatible with prior immunization for or immunity due to infection with HBV may be included at the discretion of the investigator.
• Has received a live vaccine (including attenuated) or anticipation of need for such a vaccine during the study within 3 months prior to the first dose of study drug. Note: Examples of live vaccines include but are not limited to the following: measles, mumps, rubella, chickenpox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.
• Medical or self-reported history of alcoholism within 3 months of screening.
• History of significant alcohol use within 3 months of screening, defined as regular alcohol consumption > 21 units per week for males and > 14 units for females (1 unit = 8 oz of beer or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type).
• Positive urine or breath test for ethanol or positive urine or serum screen for drugs of abuse that are not otherwise explained by permitted concomitant medications or diet.
• Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the first dose of study treatment with another investigational medication or current enrollment in another investigational drug study.
• Current treatment or treatment within 15 days or 5 half-lives (whichever is longer) before the first dose/application of study treatment with strong inducers or strong and moderate inhibitors of CYP3A4, P-gp, or BCRP (refer to the Drug Interaction Database for prohibited drugs.
• Consumption of red wine, Seville oranges, grapefruit or grapefruit juice, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices within 72 hours before the first dose of study drug.
• History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed clinically relevant by the investigator.
• Known hypersensitivity or severe reaction to povorcitinib or any excipients of povorcitinib, to ruxolitinib or any excipients of ruxolitinib or any JAK inhibitors.
• Inability to undergo venipuncture or tolerate venous access.
• History of tobacco or nicotine containing product use within 1 month of screening.
• Use of prescription drugs (including hormonal contraceptives) within 14 days of study treatment administration/application or nonprescription medications/products (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days before study treatment administration/application. However, occasional and standard dose paracetamol, acetaminophen, ibuprofen, and standard dose vitamins are permitted. Mega dose vitamins or supplements are not permissible.
• Women who are pregnant or breastfeeding.
• Any condition that would interfere with full participation in the study, including administration/application of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
• Excessive exercise (ie Iron man®, triathlon, etc) within 7 days before check-in (Day -1).
• Tattoo or scarring at skin sample sites.
• Participants prone to keloid or hypertrophic scar formation or any known wound healing disorder.
• Not willing to avoid excessive sun exposure, steam baths, sauna, swimming, and other strenuous activities for 14 days after Day 12 to ensure good tissue regeneration.
• Pronounced hairiness on the planned application sites, dOFM probe insertion sites, and skin biopsy collection sites, that may negatively affect dose application, probe placement, and/or sample testing.
• Not willing to refrain from shaving the planned application sites, dOFM probe insertion sites, and skin biopsy collection sites, or using skin care products on the planned application sites, dOFM probe insertion sites, and skin biopsy collection sites, for at least 5 days before Day 1.
• Not willing to avoid sunbathing, using tanning salons, or using spray/lotion tanning agents within 7 days prior to Day 1 dose administration/application.
• Presence of needle phobia.
• Increased risk of thrombosis (eg, personal or first-degree relative[s] history of deep vein thrombosis).

Other protocol-defined Inclusion/Exclusion Criteria may apply.