Apremilast Safety and PK Study in Recalcitrant Plaque Psoriasis

This is a phase 2, multicenter, open-label, study to evaluate the safety, tolerability,
pharmacodynamics, pharmacokinetics and efficacy of Apremilast in participants with
recalcitrant plaque-type psoriasis.

Approximately 31 participants were enrolled and received 20 mg apremilast orally BID and, in
participants who are non-responders after 84 days of apremilast, 30 mg Apremilast over the
course of the two study treatment phases. The study consisted of four phases: Screening Phase
- up to 35 days, Treatment Phase of 84 days, Extension Phase of 84 days and a Observational
Follow-up Phase of 28 days.

During the Treatment Phase, participants received two 20 mg Apremilast capsules each day.
Following the Treatment Phase, participants had the option to continue on treatment during
the Extension Phase. During the Extension Phase, participants either continued to take two 20
mg or dose escalated to two 30 mg of Apremilast each day. Participants who were considered
responders (achieved a Psoriasis Area and Severity Index (PASI-75) at the beginning of the
Extension Phase continued on 20 mg twice per day (BID) while the remaining participants
received 30 mg capsules BID. The Extension Phase was introduced after some participants had
already completed the study; therefore, there were several participants who never had the
opportunity to continue into the Extension Phase. All participants were asked to participate
in a 4-week post-treatment observational follow-up phase either upon completion of the study
or upon discontinuation of study drug for those participants who terminated the study early.

Inclusion Criteria:

Must understand and voluntarily sign an informed consent form

- Must be male or female subject of any ethnic origin or race that is >18 years at time
of consent

- Must have a documented history of plaque-type psoriasis for at least 6 months prior to
screening visit

- Subjects must fulfill criteria outlined in at least one of the following clinical
categories:

- Unresponsive to standard systemic therapy, as defined by clinical history, in the
investigator's opinion, i.e. inadequate response to one or more adequate
treatment course (s) of standard systemic therapy

- Intolerant to or cannot receive (e.g., contraindication to prescribe) standard
systemic therapy or biological interventions for psoriasis

- Must have a Static Physician Global Assessment (sPGA) score of at least 3 and a Body
surface area (BSA) ≥ 10% at screening

- Must meet the specified laboratory criteria:

o Must be able to adhere to the study visit schedule and study protocol requirements

- Females of childbearing potential (FCBP) must have a negative urine pregnancy test at
screening (Visit 1). In addition, FCBP must agree to use two of the following adequate
forms of contraception methods such as oral, injectable, or implantable hormonal
contraception; tubal ligation; intrauterine device; barrier contraceptive with
spermicide or vasectomized partner while on study. A FCBP must agree to have pregnancy
tests every 4 weeks while on study medication.

- Males (including those who have had a vasectomy) must agree to use barrier
contraception (latex condoms) when engaging in sexual activity with FCBP

Exclusion Criteria:

- History of clinically significant (as determined by the investigator) cardiac,
endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic,
immunologic, or other major disease

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study

- Pregnant or lactating females

- History of active tuberculosis (TB) infection within 3 years prior to the screening
visit. Infections which occurred > 3 years prior to entry must have been effectively
treated

- History of incompletely treated latent (as indicated by a positive PPD [purified
protein derivative] skin results) TB infection

- Clinically significant abnormality on the chest x-ray (CXR) at screening

- Psoriasis flare within 30 days of screening, as defined by protocol

- Use of systemic therapy for psoriasis within 28 days of Visit 2 (Baseline).

- Topical therapy as defined in the protocol Adalimumab, etanercept, efalizumab or
infliximab use within 56 days of Visit 2 (Baseline)

- Alefacept use within 180 days of Visit 2 (Baseline)

- Phototherapy Ultraviolet light A (UVA), Ultraviolet light B (UVB), Psoralens and
long-wave ultraviolet radiation (PUVA) within 28 days of Visit 2 (Baseline)

- Use of any investigational drug within 28 days of Visit 2 (Baseline), or 5 half lives
if known (whichever is longer) Clinically significant abnormality on 12-lead
Electrocardiogram (ECG) at screening