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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.
Full 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.
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Inclusion criteria
Individuals who meet ALL of the following criteria are eligible for participation in this study:
Exclusion criteria
Subjects are not eligible for participation in the study if any of the following criteria are met:
Females of childbearing potential not using reliable contraception, (e.g., abstinence, double barrier method, oral/implantable/transdermal contraception. Depo-provera, intrauterine device)
Female who is pregnant, lactating, has a positive serum pregnancy test drawn at the Consent/Screening Visit, or has a positive urine pregnancy test at check-in performed prior to any of the 3 Treatment Days
Presence of any uncontrolled (in the Investigator's medical opinion) systemic disease, including, but not limited to renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or psychiatric disease
History of any immune disorder, or disease/condition potentially affecting the immune system
Regular use of oral or parenteral corticosteroids (inhaled corticosteroids for stable asthma or chronic obstructive pulmonary disease are permitted)
ECG obtained at Consent/Screening Visit which shows medically significant abnormalities (e.g. bundle branch block, frequent premature ventricular contractions, corrected QT interval (QTc) prolongation >450 msec for males and >470 msec for females)
Presence of a condition that makes it unlikely that the requirements of the protocol will be completed
Urine screening test(s) positive for evidence of amphetamines, barbiturates, benzodiazepines, cocaine, methamphetamine, opiates, phencyclidine, marijuana
Positive urine cotinine test
Positive breath alcohol test
History of hypersensitivity to any formulation of abacavir
Previous treatment with any abacavir-containing product
Current participation or participation in a drug/device or biologic investigational research study within 30 days prior to the Treatment A Visit
An elective surgical or medical procedure is planned or scheduled to be performed during the period of the study
Past surgical history of any degree of gastric resection or gastric banding
History of a clinically diagnosed upper respiratory tract infection or any acute illness requiring antibiotic therapy within 14 days prior to the Treatment A Visit
Systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg or heart rate <45 bpm in a subject under the age of 40 years and heart rate <50 bpm in a subject aged ≥40 years or >100 bpm (any subject age) on repeat determinations at the Consent/Screening Visit or at check-in on the day prior to each of the 3 Treatment Days and at pre-dose if drug administered on different day than check-in
Clinical laboratory results at the Consent/Screening Visit that show any one or more of the following:
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18 participants in 5 patient groups
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Data sourced from clinicaltrials.gov
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