FTY720/cyclosporine regimens in de novo renal transplantation: a 1-year dose-finding study.
FTY720 is a novel immunomodulator being investigated for rejection prophylaxis in renal transplantation when combined with full-dose cyclosporine (CsA; FDC). This 1-year phase II study compared FTY720 plus FDC (Neoral) with FTY720 plus reduced-dose CsA (RDC) and mycophenolate mofetil (MMF) plus FDC in de novo renal transplant patients. Patients were randomized 2:2:2:1 to FTY720 5 mg plus RDC (n = 72); FTY720 2.5 mg plus RDC (n = 74); FTY720 2.5 mg plus FDC (n = 76); or MMF plus FDC (n = 39) for 12 months. CsA exposure in the RDC group was reduced on average by 50% as assessed by C(2) monitoring. The primary efficacy endpoint was the composite incidence of biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation. The incidences for this composite endpoint were 24% and 22%, respectively, for FTY720 5 mg plus RDC and FTY720 2.5 mg plus FDC versus 39% for MMF plus FDC. Patients receiving FTY720 2.5 mg plus RDC were discontinued from treatment due to risk of under-immunosuppression. FTY720 2.5 mg plus FDC and FTY720 5 mg plus RDC were safe and effective in de novo renal transplant patients over 12 months.
Mulgaonkar
S
S
Saint Barnabas Medical Center, Livingston, New Jersey, USA. smulgaonkar@sbhcs.com
Tedesco
H
H
Oppenheimer
F
F
Walker
R
R
Kunzendorf
U
U
Russ
G
G
Knoflach
A
A
Patel
Y
Y
Ferguson
R
R
D000328:Adult; D001706:Biopsy; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011409:Propylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D013110:Sphingosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine