Once-Weekly Oral Aminopterin for the Treatment of Subjects With Moderate-To-Severe Psoriasis

Exclusion Criteria

• •1. Known history of hepatitis, HIV infection, interstitial lung disease.
• •2. Greater than moderate alcohol consumption on a regular basis (moderate consumption for females is 1 drink or 1 glass of wine a day; for males is 2 drinks or 2 glasses of wine a day) and unwilling, or unable, to control consumption during the study period.
• •3. Prior use of aminopterin (AMT).
• •4. Use of these biologic treatments in the time frames specified:
• •* Within 9 months of first study drug dose: ustekinumab (Stelara).
• •* Within 12 weeks of first study drug dose: any experimental therapy for psoriasis or rheumatoid arthritis.
• •* Within 8 weeks of first study drug dose: infliximab (Remicade), adalimumab (Humira).
• •* Within 4 weeks of first study drug dose: etanercept (Enbrel).
• •* Other biologic therapies will have discontinuation periods determined by 5x their half-life.
• •5. Within 90 days prior to Day 0 and at any time while on study, the use of MTX.
• •6. Within 4 weeks prior to randomization and at any time while on study, use of phototherapy (e.g., ultraviolet B (UVB), narrow band UVB, Goeckerman regimen, Ingram regimen, PUVA), systemic medications (e.g. acitretin, mycophenolate mofetil, tacrolimus/FK506, cyclosporine A, azathioprine, 6-thioguanine, sulfasalazine, hydroxyurea, calcitriol, any systemic immunosuppressants), lithium, or any treatments that could affect psoriasis or sPGA evaluations. Subjects are eligible 4 weeks after the last dose of any of the aforementioned treatments was received.
• •7. Within 2 weeks prior to randomization and at any time while on study, use of any topical medications or treatments that could affect psoriasis evaluations (e.g., corticosteroids, anthralin, vitamin D3/calcitriol and analogues such calcipotriene and tacalcitol, synthetic retinoids such as tazarotene, coal tar, and keratolytics such as salicylic acid, lactic acid and urea including those contained in over-the-counter medicated shampoos). Subjects are eligible 2 weeks after the last dose of any of the aforementioned treatments was received.
• •Note: Over-the-counter topical steroids will be permitted for use limited to the face, axilla, and/or genitalia, as needed. These topical medications should not be used within approximately 24 hours prior to study visits Day 0 and Day 98. Over-the-counter shampoos for the treatment of psoriasis of the scalp are also permitted.
• •8. Use of emollients on the morning of the first (Week 0) study visit.
• •9. Within 2 weeks prior to Study Day 0, or on Study Day 0, or at any time during the study, use of any of the following medications that may result in drug/drug interactions with AMT: trimethoprim with or without sulfamethoxazole; sulfonamides; sulfonylureas; pyrimethamine; tromethamine; salicylates; non-steroidal anti-inflammatory (NSAID) drugs including ibuprofen; dipyridamole; colchicine; probenecid; aminoglycosides; theophylline; phenytoin; and folinic acid (i.e., leucovorin).
• •10. Known concurrent malignancy except basal or squamous cell skin carcinoma, or cervical carcinoma in situ.
• •11. Concurrent participation in another clinical trial involving experimental treatment within 30 days of Study Day 0.
• •12. Current and uncontrolled infection, cardiovascular, renal, pulmonary, hepatic or GI conditions that will interfere with the conduct of the trial or pose a morbid risk.
• •13. Investigator's opinion that a concurrent disease or condition impairs the subject's ability to complete the trial: includes psychological, familial, sociological, geographical or medical conditions.
• •14. Breast-feeding.