A Study to Evaluate the Pharmacokinetic Exposure of 2 Formulations of Apremilast in Healthy Adults
Condition: Healthy Volunteers
Intervention: Apremilast IR; Apremilast XL
Intervention description: Apremilast immediate release tablet; Apremilast extended release formulation tablet
Intervention MeSH terms: Thalidomide; Apremilast
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 144.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy Subjects; Apremilast; Pharmacokinetic

Summary:

      The purpose of this study is to evaluate the relative bioavailability of apremilast
      once-daily formulation relative to a twice daily formulation when administered as multiple
      doses (Part 1), and when administered as a single dose under fasting and fed conditions (Part
      2). Information on safety and tolerability will also be obtained.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study (Part 1 and Part
        2):

          1. Must understand and voluntarily sign a written Informed consent form (ICF) prior to
             any study-related procedures being performed.

          2. Must be able to communicate with the investigator, understand and comply with the
             requirements of the study, and agree to adhere to restrictions and examination
             schedules.

          3. Male and female subjects of any race between 18 to 55 years of age (inclusive), and in
             good health as determined by the Investigator at the time of signing the informed
             consent document.

          4. Have a body mass index (BMI) between 18 and 33 kg/m^2 (inclusive).

          5. No clinically significant laboratory test results as determined by the investigator.

          6. At the screening visit, must be afebrile, with supine systolic blood pressure (BP): 90
             to 140 mmHg, supine diastolic BP: 50 to 90 mmHg, and pulse rate: 40 to 110 bpm.
             Eligibility criteria for vital signs performed during check-in and/or predose on Day 1
             will be at the discretion of the Investigator.

          7. Must have a normal or clinically acceptable 12-lead electrocardiogram (ECG). Subjects
             must have a QT interval corrected using the Fridericia formula (QTcF) value ≤ 450
             msec.

          8. Female subjects

               1. Must have a negative pregnancy test

               2. If postmenopausal: must have follicular stimulating hormone (FSH) test result >
                  40 IU/L and a negative pregnancy test

          9. Contraception Requirements:

             Must comply with the following acceptable forms of contraception. All Female of child
             bearing potential (FCBP)1 must use one of the approved contraceptive options as
             described below while taking apremilast and for at least 28 days after administration
             of the last dose of the apremilast. At the time of study entry, and at any time during
             the study when a FCBP's contraceptive measures or ability to become pregnant changes,
             the Investigator will educate the subject regarding contraception options and the
             correct and consistent use of effective contraceptive methods in order to successfully
             prevent pregnancy.

             All FCBP must have a negative pregnancy test at Screening and Day -1 of each Treatment
             Period. All FCBP subjects 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 non-latex condom NOT made out of natural [animal] membrane [for
             example, polyurethane]); Plus one additional barrier(c) contraceptive sponge with
             spermicide.

             Male subjects (including those who have had a vasectomy) who engage in activity in
             which conception is possible must use barrier contraception (latex or non-latex
             condoms NOT made out of natural [animal] membrane [for example, polyurethane]) while
             on Investigational Product (IP) and for at least 28 days after the last dose of IP.

         10. Must agree to refrain from donating sperm, blood or plasma (other than for this study)
             while participating in this study and for at least 28 days after the last dose of
             investigational product.

         11. Subject is willing and able to adhere to the study visit schedule and other protocol
             requirements.

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment:

          1. History of any clinically significant and relevant neurological, psychiatric,
             gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic,
             endocrine, hematological, allergic disease, drug allergies, or other major disorders.

          2. Any condition which places the subject at unacceptable risk if he were to participate
             in the study, or confounds the ability to interpret data from the study.

        1 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).

        3. Use of any prescribed systemic or topical medication within 30 days of the first dose
        administration (exception, FCBP may use hormonal contraception).

        4. Use of any non-prescribed systemic or topical medication (including vitamin/mineral
        supplements, and herbal medicines) within 14 days of the first dose administration.

        5. Any surgical or medical condition possibly affecting drug absorption, distribution,
        metabolism and excretion, eg, bariatric procedure, colon resection, irritable bowel
        syndrome, Crohn's disease, etc. Subjects with cholecystectomy and appendectomy may be
        included.

        6. Exposure to an investigational drug (new chemical entity) within 30 days prior to the
        first dose administration or 5 half-lives of that investigational drug, if known (whichever
        is longer).

        7. Donated blood or plasma within 8 weeks before the first dose administration to a blood
        bank or blood donation center.

        8. History of drug abuse (as defined by the current version of the Diagnostic and
        Statistical Manual [DSM]) within 2 years before dosing, or a positive drug screen
        reflecting consumption of illicit drugs.

        9. History of alcohol abuse (as defined by the current version of the DSM) within 2 years
        before dosing, or a positive alcohol screen.

        10. Known to have hepatitis, or known to be a carrier of the hepatitis B surface antigen
        (HBsAg) or hepatitis C antibody (HCV Ab), or have a positive result to the test for human
        immunodeficiency virus (HIV) antibodies at screening.