Clinical trial: Apremilast - Oral Lichen Planus Trial (NCT03836885)

Eligibility criteria:
Inclusion Criteria:

        Each participant must meet all of the following inclusion criteria to participate in this
        study:

          1. Must be 18 years or older at time of consent.

          2. Patients must have clinically active OLP that is being considered for systemic
             therapy; and an oral biopsy within the last 12 months of randomization showing a
             lichenoid reaction correlating clinically with OLP.

          3. Must have failed topical corticosteroids therapy. Topical corticosteroid failure is
             defined as receiving a trial of at least 4 weeks of high potency topical
             corticosteroids without achieving sufficient improvement by patients.

          4. Must be in general good health (except for disease under study) as judged by the
             Investigator, based on medical history, physical examination, clinical laboratories,
             and urinalysis. (NOTE: The definition of good health means a subject does not have
             uncontrolled significant co-morbid conditions). Laboratory work-up includes the
             following: complete blood count (CBC), creatinine, albumin, aspartate aminotransferase
             (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin,
             serum, Beta-HCG (if female), Hepatitis C antibodies and HgbA1C.

          5. Male participants must use a recognized effective method of contraception with any
             female partner (i.e. at a minimum, barrier plus an additional method of contraception)
             while on investigational product and for at least 4 weeks after taking the last dose
             of investigational product.

          6. Female participants of childbearing potential (FCBP)† must have a negative pregnancy
             test at Screening. While on investigational product and for at least 4 weeks 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:

               1. Option 1: Any one of the following highly effective methods: hormonal
                  contraception (oral, injection, implant, transdermal patch, vaginal ring);
                  intrauterine device (IUD); tubal ligation; prior hysterectomy; prior bilateral
                  oophorectomy or salpingo-oophorectomy; or partner's vasectomy;

                  OR

               2. 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 1) has
                       not undergone a hysterectomy (the surgical removal of the uterus) or
                       bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not
                       been postmenopausal for at least 24 consecutive months (that is, has had
                       menses at any time during the preceding 24 consecutive months).

                    -  The female subject's chosen form of contraception must be effective by the
                       time the female subject is randomized into the study (for example, hormonal
                       contraception should be initiated at least 28 days before randomization).

        Exclusion Criteria:

        All participants meeting any of the following exclusion criteria at baseline will be
        excluded from participation in this study:

          1. Inability to give written consent by the patient or alternative decision maker (will
             be assessed at screening visit).

          2. Unwillingness to use at least one effective method of contraception due to unknown
             fetal risks

          3. Use of systemic or topical therapy for OLP other than allowed concomitant care for
             symptomatic relief in the past 4 weeks.

          4. Hypersensitivity to Apremilast or use of Apremilast within 4 weeks prior to start of
             study drug. The contraindications to Apremilast use include prior hypersensitivity
             reactions, breast-feeding, and pregnancy (Uptodate.com® accessed August 1st, 2016). An
             increased incidence of depression or depressed mood by 1.3% for Apremilast 30 mg BID
             (twice a day) (OTEZLA® drug monograph accessed August 1st, 2016) was observed in phase
             3 psoriasis studies. Celgene suggests that prescribers should carefully weigh the
             risks and benefits in patients with a history of depression and/or suicidal thoughts
             or behaviour. The research team will discuss these psychiatric adverse events in the
             screening visit where patients/caregivers will be instructed to notify the treating
             team for any mood changes.

          5. History of palpitations/tachyarrhythmia, severe renal impairment (eGFR less than or
             equal to 29), or lactose intolerance within the past 5 years. Apremilast pills contain
             lactose; however, the use of concurrent lactase enzyme in lactose intolerant
             participants will not be considered and lactose intolerant patients will still be
             excluded even if they take lactase enzyme supplementation. This is explained by the
             potential exacerbation of gastrointestinal symptoms with Apremilast as an Adverse
             Event (AE).

          6. CYP3A4 inducers have been shown to diminish Apremilast levels (Lexi-Comp Online™
             Interaction Monograph accessed August 1st, 2015); hence, patients will be excluded if
             they are on concomitant Carbamazepine, Enzalutamide, Fosphenytoin, Lumacaftor,
             Mitotane, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, and Rifapentine.

          7. As per Celgene, the presence of any of the following will exclude a subject from
             enrollment:

               1. 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.

               2. 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.

               3. 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.

               4. Pregnant or breast feeding.

               5. Active substance abuse or a history of substance abuse within 6 months prior to
                  Screening.

               6. Malignancy or history of malignancy, except for:

                    -  treated [ie, cured] basal cell or squamous cell in situ skin carcinomas;

                    -  treated [ie, cured] cervical intraepithelial neoplasia (CIN) or carcinoma in
                       situ of cervix with no evidence of recurrence within the previous 5 years.

               7. Use of any investigational drug within 4 weeks prior to randomization, or 5
                  pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).

               8. Prior treatment with apremilast
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 27-year-old woman comes to the dermatology clinic with skin rash and oral ulcers.  The rashes are mildly itchy. The patient has no other medical conditions and takes no medications.  Vital signs are normal.  On examination, there are pink papules symmetrically distributed over the anterior surfaces of the shins and ankles. There are some white ulcerated papules on her buccal mucosa. She is in relationship with her boyfriend and has only one sexual partner. Her boyfriend uses condoms. She smokes 1 to 2 cigarettes a day and drinks a beer daily. Biopsy reveals prominent hyperkeratosis with a thickened granular layer.  There is an infiltration of mononuclear cells in the superficial dermis that involves the overlying epidermis. The rete ridges have a sawtooth appearance.

Patient description (patient's own words): I went to the dermatologist because I had rashes on my skin and ulcers in my mouth. The rashes were not that itchy. I don't get it! I'm 27, I don't take medication, nor I don't have any other illnesses. My vitals were normal. My doc told me there were pink spots on the back of my throat. I'm heterosexual and have been only with my boyfriend and he uses condoms. I smoke 1 or 2 cigarettes a day and I drink a beer to accompany it. I had a biopsy and it showed some thick and grainy skin texture. The doc said it's an immune reaction.

Does the patient match the trial criteria? Contradiction