Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To evaluate the efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (tramadol/APAP) as add-on therapy for subjects with osteoarthritis (OA) pain inadequately controlled by COX-2 nonsteroidal antiinflammatory drugs (NSAID).


METHODS
This 91-day, multicenter, randomized, double-blind, placebo-controlled trial enrolled subjects with symptomatic OA for >/= 1 year who experienced at least moderate pain [visual analog scale (VAS) score >/= 50/100 mm] despite treatment with stable doses of celecoxib (>/= 200 mg/day) or rofecoxib (>/= 25 mg/day). Tramadol/APAP or matching placebo was titrated to 4 tablets/day on Day 10 and thereafter as needed up to 8 tablets/day. The primary efficacy measure was final VAS score; secondary measures included final pain relief rating scores, subject/investigator overall medication assessments, rate and time to discontinuation due to lack of efficacy, and selected quality-of-life/physical functioning scores.


RESULTS
Of 307 subjects randomized, 306 taking celecoxib (56.5%) or rofecoxib (43.5%) were included in the intent-to-treat population (n = 153 tramadol/APAP, 153 placebo). Mean final VAS scores for tramadol/APAP plus COX-2 NSAID were significantly lower than placebo plus COX-2 NSAID (41.5 vs 48.3; p = 0.025) and mean final pain relief rating scores were significantly higher (p = 0.002). Subjects taking tramadol/APAP showed significant improvements compared with placebo in subject/investigator medication assessments, as well as in the WOMAC Physical Function and the Medical Outcome Study Short Form-36 Role-Physical measures. The most common treatment-related adverse events for tramadol/APAP were somnolence (6.5%), nausea (4.6%), and constipation (3.3%). Mean tramadol/APAP dose was 4.1 tablets (154 mg tramadol/ 1332 mg APAP).


CONCLUSIONS
Tramadol 37.5 mg/APAP 325 mg combination tablets were effective and safe as add-on therapy with COX-2 NSAID for treatment of OA pain.
Emkey
Ronald
R
Radiant Research/Reading,Wyomissing, Pennsylvania 19610, USA. ronaldemkey@radiantresearch.com
Rosenthal
Norman
N
Wu
Shu-Chen
SC
Jordan
Donna
D
Kamin
Marc
M
D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007783:Lactones / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000008:administration & dosage* / Q000009:adverse effects; D010003:Osteoarthritis / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage; D013450:Sulfones; D014147:Tramadol / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D007783:Lactones; D009294:Narcotics; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C478659:Ultracet; C116926:rofecoxib; D000082:Acetaminophen; D014147:Tramadol; D000068579:Celecoxib