Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects.
OBJECTIVE
To investigate the efficacy and safety of SC-58635 (celecoxib), an antiinflammatory and analgesic agent that acts by selective cyclooxygenase 2 (COX-2) inhibition and is not expected to cause the typical gastrointestinal (GI), renal, and platelet-related side effects associated with inhibition of the COX-1 enzyme.


METHODS
Four phase II trials were performed: a 2-week osteoarthritis efficacy trial, a 4-week rheumatoid arthritis efficacy trial, a 1-week endoscopic study of GI mucosal effects, and a 1-week study of effects on platelet function.


RESULTS
The 2 arthritis trials identified SC-58635 dosage levels that were consistently effective in treating the signs and symptoms of arthritis and were distinguished from placebo on standard arthritis scales. In the upper GI endoscopy study, 19% of subjects receiving naproxen (6 of 32) developed gastric ulcers, whereas no ulcers occurred in subjects receiving SC-58635 or placebo. The study of platelet effects revealed no meaningful effect of SC-58635 on platelet aggregation or thromboxane B2 levels, whereas aspirin caused significant decreases in 2 of 3 platelet aggregation measures and thromboxane B2 levels. In all 4 trials, SC-58635 was well tolerated, with a safety profile similar to that of placebo.


CONCLUSIONS
SC-58635 achieves analgesic and antiinflammatory efficacy in arthritis through selective COX-2 inhibition, without showing any evidence of 2 of the toxic effects of COX-1 inhibition associated with nonsteroidal antiinflammatory drugs.
Simon
L S
LS
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Lanza
F L
FL
Lipsky
P E
PE
Hubbard
R C
RC
Talwalker
S
S
Schwartz
B D
BD
Isakson
P C
PC
Geis
G S
GS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001241:Aspirin / Q000627:therapeutic use; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004724:Endoscopy; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects; D010003:Osteoarthritis / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles; D012449:Safety; D012720:Severity of Illness Index; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000097:blood; D016896:Treatment Outcome
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D013929:Thromboxane B2; D009288:Naproxen; D000068579:Celecoxib; D001241:Aspirin