Bioequivalence and Pharmacokinetic Study of Prurisol™ and Abacavir Sulfate in Healthy Volunteers
Condition: Psoriasis
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 1

Summary: 
      Cellceutix Corporation has created a new chemical entity for the treatment of psoriasis,
      termed Prurisol™, which is an ester of abacavir. This first-in-human study of Prurisol
      (abacavir acetate) is being performed to evaluate the pharmacokinetics, safety and tolerance
      of a single oral doses of Prurisol administered to healthy volunteers and the bioequivalence
      to abacavir sulfate (Ziagen). This study will be followed by a 505(b)(2) Phase 2 trial in
      patients with moderate to severe plaque psoriasis.
    

Detailed description: 
      Prurisol™, abacavir acetate, is an ester of abacavir. Prurisol is believed to act as an
      immune response modifier in certain conditions, including psoriasis. Abacavir is a synthetic
      nucleoside analogue. Ziagen, abacavir sulfate, was developed and marketed as a treatment for
      HIV-1 infection for over a decade. Ziagen inhibits viral DNA synthesis. Consequently,
      Prurisol is under consideration as a possible new therapy for moderate to severe plaque
      psoriasis. The nonclinical efficacy of Prurisol has been demonstrated in the human psoriatic
      skin xenograft model in irradiated severe combined immune deficient mice. Histologic as well
      as visual observations confirmed a treatment benefit of Prurisol in this animal model.
      Interleukin-20 (IL-20) is a recently discovered cytokine displaying increased levels in
      psoriatic lesions, and levels of IL-20 have been shown to decrease with anti-psoriasis
      treatment and correlate with clinical improvement. IL-20 has been suggested as a specific
      target in psoriasis treatment. In comparison to vehicle-treated animals, the mice
      transplanted with human psoriatic tissue and treated with Prurisol had significant reductions
      in plasma IL-20 levels which were greater than those seen with methotrexate treatment. The
      expression of PRINS (psoriasis susceptibility-related RNA gene induced by stress) was
      significantly lower with twice daily Prurisol treatment compared to control.

      This study is designed as an open-label, randomized, 2-period, 2-treatment, 2-sequence,
      single-dose intensive pharmacokinetic (PK) study conducted in healthy volunteers. In
      addition, a lead-in dosing period will allow the evaluation of the PK of abacavir from 3
      escalating single doses of Prurisol (50mg, 100mg, 200mg). Completion of each dosing cohort
      will be followed by a 24-hour safety evaluation period before moving to a higher dose.
      Adverse Events, vital signs, physical examination, and safety laboratory tests (clinical
      chemistry and hematology) from each dosed cohort will be reviewed prior to any dose
      escalation for next cohort.

      For each subject completing the first part, there will be a 5 to 21 day washout period before
      the next dose of study drug. Subjects will be randomly assigned to receive either a single
      dose of 350mg Prurisol or 300mg of Ziagen in the second dosing period. After a 5 to 21 day
      washout period, subjects will receive the alternate treatment in the third dosing period.

      Blood samples for PK analysis will be obtained over a 24 hour period for each dose. Safety
      and tolerability will be assessed by ascertainment of adverse events, results of clinical
      laboratory testing and physical examination.
    

Intervention name(s): Prurisol; Ziagen
Intervention type(s): Drug; Drug
Intervention description(s): Experimental Drug; Active comparator
Other intervention name(s): abacavir acetate; abacavir sulfate
Intervention MeSH terms: Abacavir; Dideoxynucleosides
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: bioequivalence; pharmacokinetics; psoriasis