Study to Evaluate Pharmacokinetics of Apremilast in Heatlhy Male Subjects

This will be a single-center, open-label, crossover, single modified-release-dose, study in
male subjects to evaluate the pharmacokinetics of prototype modified-release formulations
compared to the reference immediate-release apremilast formulation. Subjects will be randomly
assigned to a treatment sequence. A total of up to 8 test MR formulations may be evaluated.

Group 1: 4-sequence, 4-period to compare three modified-release prototypes with the reference
immediate-release formulation. A total of 16 subjects will be enrolled to obtain at least 12
subjects who complete all 4 periods.

One of two scenarios will be conducted in the second group depending on the availability of
the modified-release formulations.

This will be a single-center, open-label, crossover, single modified-release-dose, study in
male subjects to evaluate the pharmacokinetics of prototype modified-release formulations
compared to the reference immediate-release apremilast formulation. Subjects will be randomly
assigned to a treatment sequence. A total of up to 8 test MR formulations may be evaluated.

Group 1: 4-sequence, 4-period to compare three modified-release prototypes with the reference
immediate-release formulation. A total of 16 subjects will be enrolled to obtain at least 12
subjects who complete all 4 periods.

One of two scenarios will be conducted in the second group depending on the availability of
the modified-release formulations.

Group 2/Scenario 1: This is a 4-sequence, 4-period design identical to Group 1. This will
occur if all three modified-release formulations planned for Group 2 are available. A total
of 16 subjects will be enrolled to obtain at least 12 subjects who complete all 4 periods.

Group 2/Scenario 2: This is a 6-sequence, 3-period design. This will occur if only two
modified-release formulations are tested in Group 2. A total of 18 subjects will be enrolled
to obtain at least 12 subjects who complete all 3 periods.

A third group may be enrolled to evaluate the pharmacokinetics of one or two additional
prototype formulations (after the initial six) compared to the immediate-release formulation.
One of two scenarios will be conducted in the third group depending on the availability of
the prototype formulations.

Group 3/Scenario 1: This is a 2-sequence, 2-period design that will be used if one test
formulation is available. A total of 14 subjects will be enrolled to obtain at least 12
subjects who complete both periods.

Group 3/Scenario 2: This is a 6-sequence, 3-period design identical to Group 2/Scenario 2
above. This will occur if two test formulations are available. A total of 18 subjects will be
enrolled to obtain at least 12 subjects who complete all 3 periods.

A fourth group may be enrolled to evaluate the PK of four additional prototype formulations
compared to the IR formulation.

Group 4: This is a 10-sequence, 5-period William Square design to compare four MR prototypes
with the reference IR formulation. A total of 30 subjects will be enrolled to obtain at least
20 subjects who complete all 5 periods.

Inclusion Criteria:

- Subjects must satisfy ALL of the following criteria to be eligible for enrollment into
the study:

1. Must understand and voluntarily sign a written informed consent form 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 subjects of any race between 18 to 55 years of age (inclusive), and in good
health as determined by the Investigator.

4. Has a body mass index between 18 and 33 kg/m2 (inclusive).

5. No clinically significant laboratory tests as determined by the investigator.

6. Must not have a fever, with systolic blood pressure: 90 to 140 mmHg and diastolic
blood pressure: 60 to 90 mmHg, and pulse rate: 40 to 110 bpm (measurements taken
while lying down).

7. Must have a normal or clinically acceptable 12-lead ECG.

8. Subjects (including those who have had a vasectomy) who engage in activity in
which conception is possible must use barrier contraception (male latex condom or
non-latex condom not made out of natural [animal] membrane [eg, polyurethane])
while on study medication, and for 28 days after the last dose of study
medication.

9. 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 study drug.

Exclusion Criteria:

- The presence of ANY of the following will exclude any healthy subject from enrollment
into the study:

1. History of any clinically significant and relevant neurological,
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.

3. Use of any prescribed systemic or topical medication within 30 days of the first
dose administration, unless Sponsor agreement is obtained.

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, unless Sponsor agreement is obtained.

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 cholecytectomy 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 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 serum hepatitis, or known to be a carrier of the HBsAg, or HCV Ab,
or have a positive result to the test for HIV antibodies at Screening.