Ensayos clínicos

Inclusion Criteria:

• Male and female subjects between 18 and 70 years of age.
• Oral ulcers that occurred at least monthly in the 6 month period prior to enrollment.
• Had at least 2 oral ulcers in the 4 weeks prior to enrollment at baseline.
• At least 3 oral ulcers during an ulcer flare.
• Patients must be candidates for systemic therapy for the treatment of oral ulcers, those that are considered unsuitable for topical therapy alone based on severity of disease, or whose oral ulcers cannot be adequately controlled with topical therapy.
• Female premenopausal subjects must use one of the approved contraceptive options while taking apremilast and for at least 28 days after administration of the last dose of apremilast.
• Patients are able and willing to provide written informed consent after the nature of the study is fully explained.
• No evidence of systemic disease.
• Contraception requirements:
  • Females of childbearing potentiala (FCBP) must have a negative pregnancy test at screening and baseline.  While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below:
    • Option 1 - Any one of the following highly effective methods:  hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner’s vasectomy;
  • OR
    • Option 2 - Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]; PLUS one additional barrier method:
      • (a) diaphragm with spermicide;
      • (b) cervical cap with spermicide; or
      • (c) contraceptive sponge with spermicide.
  • A female of childbearing potential is a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy or has not been postmenopausal for at least 24 consecutive months.

Exclusion Criteria:

• Prior use of apremilast.
• Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
• Having received concomitant immune modulating therapy 12 weeks prior to enrollment, systemic steroids 6 weeks prior to enrollment or topical steroids within 4 weeks prior to enrollment.
• Pregnant women or breast-feeding mothers.
• Systemic or opportunistic fungal infection.
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (tuberculosis and atypical mycobacterial disease, hepatitis B and C and herpes zoster, histoplasmosis, coccidiomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of the screening phase.
• History of positive test for, or any clinical suspicion of, human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency.
• History of depression.
• Malignancy or history of malignancy, except for:
  • a - treated (i.e., cured) basal cell or squamous cell in situ skin carcinomas;
  • b - treated (i.e., cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of cervix  with no evidence of recurrence within the previous 5 years.
• Other than disease under study, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major disease that is currently uncontrolled.
• Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.
• Prior history of suicide attempt at any time in the subject’s life time prior to screening or randomization, or major psychiatric illness requiring hospitalization within the last 3 years.
• Active substance abuse or a history of substance abuse within 6 months prior to screening.
• Presence of any of the following vitamin deficiencies - B1, B2, B6, B12, vitamin C, zinc, folate, iron.
• Celiac disease.
• Inflammatory Bowel Disease.
• Genital aphthous ulcers.
• Behçet’s disease.
• History of positive patch test for allergic contact stomatitis.
• Positive anti-endomysial or anti-gliadin antibodies.
• A diagnosis of uveitis (current or previous).
• Erythema nodosum-like lesions (current or previous).
• An established diagnosis of a systemic disease (SLE, Reiter’s, Sweet’s and MAGIC syndrome).