Clinical trial NCT02647086 (phase 1, status: completed)
Conditions: atopic dermatitis
ICD codes: L20.89, L20.9
Drugs: dupilumab, midazolam, omeprazole, warfarin, caffeine, metoprolol
SMILES: CCO, CC1=CC(O)=CC(C)=C1Cl, [Na+].OC([O-])=O, S1SSSSSSS1, CN1C=NC2=C1C(=O)N(C)C(=O)N2C, COCCC1=CC=C(OCC(O)CNC(C)C)C=C1
Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patient, aged 18 years or older

          2. Diagnosis of Chronic AD, defined as diagnosis of AD for at least 3 years before the
             screening visit

          3. Eczema Area Severity Index (EASI) score ≥16 at the screening and baseline visits

          4. Investigator's Global Assessment (IGA) score ≥3 (on the 0 to 4 IGA scale) at the
             screening and baseline visits

          5. ≥10% Body Surface Area (BSA) of AD involvement at the screening and baseline visits

          6. Patients with documented recent history (within 6 months before the screening visit)
             of inadequate response to outpatient treatment with topical medications, or for whom
             topical treatments are otherwise medically inadvisable (eg, because of important side
             effects or safety risks)

          7. Provide signed informed consent

        Exclusion Criteria:

          1. Prior participation in a dupilumab clinical trial

          2. The use of any of the following treatments within 4 weeks before the baseline visit:

               -  Systemic corticosteroids

               -  Immunosuppressive/immunomodulating drugs

               -  Phototherapy for AD

          3. Administration, within 14 days before baseline or within a period of 5 times the
             elimination half-life of the medication before baseline, whichever is longer, of any
             medication that is a known inducer or inhibitor of either one or more of the following
             CYP enzymes: CYP3A, CYP2C19, CYP2C9, CYD2D6, and CYP1A2. Patients who are on any of
             these medications at the time of screening and cannot be safely taken off these
             medications will be excluded from the study.

          4. Any contraindication to one or more of the following drugs, according to the
             applicable labeling:

               -  Midazolam

               -  Omeprazole

               -  Warfarin

               -  Caffeine

               -  Metoprolol

          5. Consumption of any 1 or more of the following food items and/ or beverages within 1
             week prior to baseline:

               -  Grapefruit or grapefruit juice, apple or apple juice, orange or orange juice,
                  lemons or lemon juice, limes or lime juice

               -  Vegetables from the mustard green family (eg, broccoli)

               -  Charbroiled meats

               -  Caffeinated beverages, foods or drugs containing caffeine Patients who are not
                  willing to abstain from the consumption of these food items and/or beverages for
                  certain periods during the study will also be excluded

          6. History of excessive consumption of beverages containing caffeine (more than 4 cups or
             glasses per day). Patients who are not willing to abstain from the consumption of
             caffeine during certain periods of the study will also be excluded

          7. History or presence of alcohol or drug abuse within last 2 years

          8. History of smoking within last 2 years

          9. Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping

         10. Presence of any one or more of the following lab abnormalities at screening:

               -  Platelet count ≤100 x 10^3/µL

               -  Neutrophils ≤1 x 10^3/µL

               -  Creatinine phosphokinase (CPK) >10 x upper limit of normal (ULN)

               -  International normalized ratio (INR) ≥2

         11. Active chronic or acute infection requiring treatment with systemic antibiotics,
             antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit,
             or superficial skin infections within 1 week before the screening visit

         12. Known or suspected immunodeficiency, including history of invasive opportunistic
             infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis,
             pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent
             infections of abnormal frequency or prolonged duration suggesting an immune
             compromised status, as judged by the investigator

         13. History of human immunodeficiency virus (HIV) infection or positive HIV serology at
             screening

         14. Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb),
             or hepatitis C antibody (Hep C Ab) at the screening visit. NOTE: Patients who are
             HBsAg negative and HBsAb positive are considered immune after a natural infection has
             cleared or they have been vaccinated against hepatitis B. Therefore, they are
             acceptable for the study.

         15. History of malignancy within 5 years before the baseline visit, except completely
             treated in situ carcinoma of the cervix, and completely treated and resolved
             non-metastatic squamous or basal cell carcinoma of the skin

         16. History of clinical endoparasitosis (ie, helminth infection) within 12 months before
             the baseline visit, or high risk of helminth infection, such as residence within or
             recent travel (within 12 months before the baseline visit) to areas endemic for
             endoparasitoses, where the circumstances are consistent with parasite exposure (eg,
             extended stay, rural or slum areas, lack of running water, consumption of uncooked,
             undercooked, or otherwise potentially contaminated food, close contact with carriers
             and vectors, etc), unless subsequent medical assessments (eg, stool exam, blood tests,
             etc) have ruled out the possibility of parasite infection/infestation

         17. Female patients who are pregnant, breastfeeding, or planning to become pregnant or
             breastfeed during the study

         18. Women who are using any form of hormonal contraceptives (eg, oral, injectables,
             implants, patches, rings, hormone-impregnated intrauterine devices [IUDs]) for birth
             control

         19. Women unwilling to use adequate birth control, if of reproductive potential and
             sexually active.