Apremilast Safety and PK Study in Recalcitrant Plaque Psoriasis

A Phase 2, Open-label Multi-center Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of Apremilast in Subjects With Recalcitrant Plaque-type Psoriasis

The study will test the safety and tolerability of Apremilast twice a day in participants with recalcitrant plaque type 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