title: A multicenter, randomized, double-blind study comparing different FK778 doses (manitimus) with tacrolimus and steroids vs. MMF with tacrolimus and steroids in renal transplantation.
abstract: BACKGROUND
  This multicenter phase II study in renal transplantation compared 3 concentration-controlled ranges of FK778 (manitimus) with mycophenolate mofetil (MMF) both given in combination with tacrolimus and corticosteroids.
  
  
  METHODS
  364 patients were randomized to 12-month treatment: high-level FK778 group (H, N=87) received 4 x 600 mg/day (4 days) followed by 120 mg/day; mid-level FK778 group (M, N=92) received 3 x 600 mg/day (3 days) followed by 110 mg/day, low-level FK778 group (L, N=92) received 2 x 600 mg/day (2 days) followed by 100 mg/day, and control group received MMF 1 g/day (MMF, N=93). After week 6, FK778 doses were adjusted to trough ranges of 75-125 μg/mL (H), 50-100 μg/mL (M) and 25-75 μg/mL (L). Tacrolimus and steroids were administered at the same dose in each of the 4 groups.
  
  
  RESULTS
  Biopsy proven acute rejection (BPAR) at 24 weeks, the primary study endpoint, was comparable in the L (22.8%) and MMF (17.2%) groups but higher in the H (34.5%) and M (29.3%) groups. BPAR at 12 months was comparable in the L (23.9%) and MMF (19.4%) groups but higher in the H (34.5%) and M (31.5%) groups. Graft and patient survival were lowest in the H group and renal function was poorest in the H and M groups. Premature study withdrawal was highest in the H group.
  
  
  CONCLUSIONS
  Efficacy was similar between the low-level FK778 and MMF groups. Increased FK778 exposure was poorly tolerated and did not improve efficacy.
authors: Klinika Transplantologii, Szpital Uniwersytecki, Bydgoszcz, Poland. zwlodar@yahoo.co.uk
authors: Zbigniew
authors: Z
authors: Wlodarczyk
authors: Yves
authors: Y
authors: Vanrenterghem
authors: Bernhard K
authors: BK
authors: Krämer
authors: Jean-Paul
authors: JP
authors: Squifflet
authors: Marek
authors: M
authors: Ostrowski
mesh_terms: D000328:Adult; D000480:Alkynes / Q000008:administration & dosage* / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D007555:Isoxazoles / Q000008:administration & dosage* / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D009570:Nitriles / Q000008:administration & dosage* / Q000097:blood; D013256:Steroids / Q000008:administration & dosage* / Q000097:blood; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000480:Alkynes; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D009570:Nitriles; D013256:Steroids; C115284:2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide; D009173:Mycophenolic Acid; D016559:Tacrolimus